A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE
Brain Tumors Bookmark and Share

Brain Tumor Program

City of Hope is a leader in the diagnosis, treatment and research of brain cancers and tumors. Our specialized brain tumor program takes a comprehensive, patient-centered approach to treating a broad variety of tumors, including:
 
  • Gliomas
    • Astrocytomas
    • Oligodendrogliomas
    • Ependymomas
    • Mixed gliomas
    • Glioblastoma multiforme
  • Meningiomas
  • Medulloblastomas
  • Schwannomas
  • Craniopharyngiomas
  • Secondary brain tumors (metastases from other cancers)
  • Benign tumors in the brain and surrounding tissues (such as the pituitary gland )
 
Our multidisciplinary team of health care professionals take an integrated approach to treating this disease by combining the latest research findings with outstanding patient care. This includes using advanced technologies and specialized techniques such as:
 
  • minimally-invasive surgical techniques minimally-invasive surgical techniques that can remove the tumor with less impact to the surrounding healthy brain tissue; our neurosurgeons’ expertise in biopsy and resection also means they can access and treat brain tumors that are considered inoperable elsewhere
  • Tumor Treating Fields therapy, which uses an alternating, low current electric field to block and reverse brain tumor growth by interfering with tumor cell division
  • highly precise radiation therapy  that can target tumor sites with minimal exposure to nearby tissues
  • targeted drugs and drug combinations that can treat hi-grade tumor with greater effectiveness and fewer side effects
 

New Clinical Study for Recurrent Glioblastoma Being Conducted at City of Hope

Neural Stem Cells (NSCs) have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
IRB# 13401: A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified NSCs. These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU. The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please call 626-471-9393 or email at neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 

 
Additionally, City of Hope patients have access to our extensive team of supportive care experts — including rehabilitation specialists, palliative care physicians and clinical social workers. Working closely with the patient’s primary care team, they can detect and address quality of life issues related to brain tumor diagnosis and treatments. This includes  managing symptoms (such as nausea, fatigue and cognitive effects), maintaining quality of life throughout treatment and adjusting to a post-treatment lifestyle.
 
Learn more about brain tumor types, symptoms, risk factors and diagnostic tests on National Cancer Institute’s website.
 
 
 
As one of a handful of institutes to attain the elite designation of Comprehensive Cancer Center by the National Cancer Institute, City of Hope is acknowledged as a leader in research and treatment of brain tumors. With our decades of experience, specialized therapy protocols and extensive program of clinical trials, newly diagnosed or relapsed patients can find a treatment regimen that is tailored to their needs and gives them the best chance for survival. U.S. News & World Report also named City of Hope as one of the top cancer hospitals in the country.
 
 
If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about  becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.
 
 
 
 
 

Brain Tumor Team

Our Treatment Approach to Brain Tumors

City of Hope has one of the most renowned brain tumor programs in the United States, with a multidisciplinary team of medical experts across different fields including surgery, radiation oncology, medical oncology and supportive care medicine. Together, they work collaboratively to plan and implement a treatment regimen that is individually tailored to the patient to improve survival chances, enhance outcomes, minimize side effects and boost quality of life.

Surgery

For operable brain tumors, surgical removal of the cancer is typically the first treatment provided and can be curative for early stage patients. However, it is also a viable option for patients with advanced or high-grade tumors, significantly improving outcomes and quality of life. Our neurosurgery team’s focus on researching and treating brain tumors also means they can target tumors that are considered inoperable elsewhere.
 
City of Hope’s neurosurgeons also specialize in minimally invasive procedures whenever possible. By using fewer incisions and making smaller cuts, our surgeons can remove and extract the tumor with minimal impact to the surrounding healthy brain tissue. As a result, patients experience less discomfort, fewer post-surgical complications and a faster recovery time.
 
These procedures include:
 
  • Intraoperative cortical mapping: This technology gives the surgeon a computerized map of key brain regions, including speech, motor and sensory centers. By avoiding these critical areas, the risk of neurological damage is minimized while allowing as much of the tumor to be removed as possible.   
  • Image-guided surgical navigation: This technology helps guide the removal of tumors that are difficult to visualize or are located in “high-risk” areas of the brain by using preoperative magnetic resonance images (MRIs).
  • Endoscopic surgery: Certain brain surgery procedures may be performed through an endoscope - a thin, lighted tube that requires a small opening and accommodates tiny surgical tools. Smaller openings minimize postoperative discomfort and risk of infection. City of Hope researchers are working to develop a miniaturized surgical system that will allow brain surgeries to be even less invasive, with an even lower risk of complications.
 
Our neurosurgeons also work closely with radiation and medical oncologists so that multiple treatments can be performed in one procedure. For example, after resection they can apply chemotherapy directly to the surgery site, which can kill remaining tumor cells and reduce the likelihood of recurrence.
 

Radiation Therapy

For some brain tumors — particularly those that cannot be treated with surgery — radiation can target and kill brain tumor cells, improving survival outcomes and providing symptom relief.
Radiation may also be performed after surgery to kill any remaining abnormal cells at the tumor site, or combined with chemotherapy to improve the effectiveness of both therapies.
 
In addition to standard radiation regimens, City of Hope also offers Helical TomoTherapy, an advance technology combining radiation delivery with advanced imaging. This allows the radiation beams to be “sculpted” to the tumor’s size and shape, resulting in more focused radiation on the cancer site while minimizing exposure to adjacent tissues and organs. This can reduce the likelihood and severity of side effects, as well as preserving cognitive function.
 

Alternating Electric Field Therapy

Brain tumor patients at City of Hope may be treated by the recently approved alternating electric field therapy (also known as tumor treating fields or TTF.) This treatment targets and attacks tumor cells through an alternating, low-intensity electrical field, blocking tumor cell division processes.
 
The therapy is non-invasive (the current-producing transducers are placed directly on the skin around the tumor region) and is portable, allowing patients to be continuously treated while they go about their normal activities throughout the day.

Drug Therapy

City of Hope uses a wide range of chemotherapy, targeted therapy and immunotherapy drugs to treat brain tumors. These drugs may be taken orally, intravenously (injected into the bloodstream) or applied directly at the tumor site during surgery.
 
In addition to standard drug regimens, patients have access to newly developed drugs (or drug combinations) through our clinical trials program.
 
These drugs can also enhance the effectiveness of other brain tumor treatments by shrinking the tumor beforehand — making it easier to extract with surgery or target with radiation — or lowering chances of recurrence afterwards by targeting and attacking any remaining tumor cells.
 
As part of the treatment team, a medical oncologist will evaluate the patient’s cancer, health and other factors, so that the drug therapy regimen can be tailored to the patient throughout the continuum of care.
 

Become a Patient

If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.

Brain Tumor Clinical Trials

City of Hope currently has many clinical trials in progress, a number of which address malignant brain tumors. Clinical trials offer patients new and promising experimental treatments not available elsewhere. In fact, nearly one in two patients at City of Hope is part of a clinical trial. These trials evaluate the safety and efficacy of prospective therapies. Participants in clinical trials receive excellent care and are closely monitored. We encourage all brain tumor patients to participate in clinical trials since that will enable us to find better treatments for brain tumors.
 
 
For more information about the studies listed below including eligibility criteria, please call: 626-471-9393. For a summary of these studies including eligibility criteria, visit the City of Hope clinical trials website.
 
Newly Diagnosed
 
11180  
A Phase III Clinical Trial Evaluating DCVax®-Brain, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma
                                                                                                                                   
Recurrent Disease
 
13401
A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
Neural Stem Cells have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified neural stem cells (NSCs).  These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU.  The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please call 626-471-9393 or email neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 
13116
A Phase I Gene Therapy Trial of the Safety and Tolerability of Toca 511 in patients Recurrent High Grade Glioma
 
LEARN MORE ABOUT THE TOCA 511 & TOCA FC STUDIES
TOCA 511 & TOCA FC mechanism
This is a very exciting new experimental gene therapy treatment for high grade brain tumors. The basic concept is that a virus (Toca 511) is injected into the tumor. This virus was designed to infect only the brain tumor cells and leave the normal cells alone. When it infects a cell, it adds a gene to the cell which encodes for an enzyme that can convert an antibiotic drug (Toca FC) into a toxic chemotherapy (5-FU), selectively in the tumor. This drug (Toca FC) is given orally every few weeks, and it kills the tumor cells that have enough copies of this enzyme to convert Toca FC to 5-FU. The tumor cells that are infected but don't have enough of the enzyme act as a reservoir - they start the process over again - spreading the infection for a few more weeks, and these cycles are repeated over and over again until the entire tumor is potentially gone.
 
If you were diagnosed with Recurrent High Grade Glioma (HGG) (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma) that have increased in size following treatment with surgery, radiation therapy and temozolomide. The Toca 511 and Toca FC studies might be the studies for you.
 
Who can participate in the Toca 511 & Toca FC studies? You may qualify for a Toca 511 & Toca FC study if you:
 
  • Are at least 18 years old (upper limit of 80 years in one of the studies)
  • Have recurrent HGG
     
Your doctor will be able to review with you these and other eligibility criteria. For more information about the Toca 511 & Toca FC studies, please contact Jana Portnow M.D. or Behnam Badie M.D. at  626-471-9393 or visit www.tocagen.com.
 
Non-Therapeutic
 
11320
Feasibility of Intraoperative Optical Imaging and Spectroscopy in Brain Tumors
 
13459
Phase 2, Open-Label, Imaging Trial of I-124-CLR1404 in Patients with Newly Diagnosed or Recurrent Glioblastoma Multiforme. (CELLECTAR)

Brain Tumor Research


There is extensive collaboration between City of Hope clinicians and researchers to develop and evaluate new cancer therapies designed to improve survival and quality of life outcomes. City of Hope patients have access to a wide variety of clinical trials ranging from new chemotherapy and targeted therapies, novel surgical techniques, new radiation approaches and strategies to minimize side effects and chances of cancer recurrence.
 
Our current brain tumor research efforts include:
 
IMMUNOTHERAPY

Unlike drugs that act by chemically killing cancer cells or halting their growth, immunotherapy uses the body’s own immune system to trigger its ability to seek out and kill cancer. City of Hope scientists are working on several immunotherapy approaches designed to exploit the body’s natural defenses against the disease:

Nanotubes: Small and Lethal Envelopes Used to Kill Cancer

Nanotubes are microscopic technology shaped into tiny tubes about 1/10,000th the width of a human hair.  Behnam Badie, M.D., is working closely with Jacob Berlin, Ph.D., to use nanotubes to deliver a drug called CpG, which activates immune cells called macrophages to recognize and attack tumor cells. Because nanotubes can carry the drug directly to macrophages around the tumor, patients can receive stronger dosages, tolerate their therapy better and recover more quickly.
Principal investigators: Behnam Badie, M.D.; Jacob Berlin, Ph.D. and Leying (Larry) Zhang, Ph.D.
 
 
Nanoparticles: Guiding Cancer Treatment to the Tumor with Magnets

Behnam Badie, M.D., is collaborating with scientists at Caltech to design a dynamically programmable, low-intensity magnetic field to route and traffic macrophages that have been treated with CpG to tumor sites. In this method, patients would receive CpG-loaded nanoparticles engineered with an iron oxide, so that the macrophages become magnetic.  The magnetic field is generated by a grid, which allows for control over the spatial and temporal profile. Dr. Badie believes that directing CpG-treated macrophages to the areas where they are needed will make this treatment approach even more effective and durable.
Principal investigator: Behnam Badie, M.D.
 
Macrophages and Microglia: Harnessing the Immune System's Clean-up Crew

Macrophages are immune cells that act as scavengers feeding upon dead cells, foreign substances, and other debris in the body. Microglia are macrophages specific to the central nervous system. Microglia are normally inactive but become activated in response to inflammation, infection and trauma. Once activated, they proliferate and migrate to the site of injury. Behnam Badie, M.D., is researching ways to improve outcomes in post-surgical brain tumor patients by re-engineering the microglia to deliver therapeutic agents to the tumor site, killing residual tumor cells. He also aims to extend the life of T cells using microglia and test their efficacy against cancer. This study will likely garner results within a year, setting the stage for Phase I clinical trials.
Principal investigators: Behnam Badie, M.D. , and Leying (Larry) Zhang, Ph.D.
 
T cells: Maximizing a Patient's Immune System

The Cellular Immunotherapy program, led by Stephen J. Forman, M.D., F.A.C.P. , chair, Hematology & Hematopoietic Cell Transplantation, continues to develop innovative treatments that reduce the need for harsh radiation and chemotherapy. One of the most exciting programs underway at City of Hope, the cellular immunotherapy program is developing technology to take T cells from a cancer patient and reprogram them through genetic engineering to target and eradicate the patient’s cancer.
 
Using pioneering technology, we have been able to isolate immune cells from a patient’s blood sample and then engineer those cells to express an artificial receptor that will seek out and attack cancer cells. In the lab, our researchers then grow billions of identical, reprogrammed T cells. In the clinic, the T cells are re-infused into the patient, where they go to work eliminating the cancer. Under Forman’s leadership, City of Hope has conducted the first-ever FDA-authorized clinical trials using reprogrammed T cell therapy for lymphoma, neuroblastoma and glioma.
 
In the glioma study currently underway, patients are infused with engineered T cells that respond to an antigen called CD8. An antigen is any foreign substance to which the body reacts by dispatching antibodies such as T cells. These reprogrammed T cells act as homing devices to take the body’s T cells to the cancer. Although only glioma patients were initially targeted for treatment, researchers have plans to expand this therapy to another brain tumor, medulloblastoma, in pediatric patients.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 2 T cells: Universal T cells

One prong of research seeks to formulate a T cell that is protected from rejection by the patient’s own immune system, thus becoming a potential “universal T cell” for patients everywhere. Specifically, Generation 2 T cells are programmed to be accepted without triggering a rejection reaction. By developing such a T cell, our researchers thus create a means to mass produce T cells from one patient on behalf of thousands more. The first glioma patient treated with Generation 2 T cells was in 2007 — the first in the world to be treated with this novel therapy.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 3 T-cells: Stacking the Deck Against Cancer

While City of Hope researchers develop the autoimmune-resistant T cell, they plan to adapt it to create Generation 3 T cells. The goal is to develop technology that enables researchers to equip Generation 2 T cells with additional cancer-fighting therapeutic material to strengthen their impact against cancer. John Rossi, Ph.D., chairman and professor of Molecular Biology at City of Hope, and Forman are using interfering ribonucleic acid (RNAi) inside T cells to make them even more effective cancer combatants. A drug using RNAi is set for clinical trials.
Principal investigators: Stephen J. Forman, M.D., F.A.C.P. , and John Rossi, Ph.D.
 
 
STEM CELL THERAPY
 
Neural Stem Cells: One-Way Tickets to Tumors

Neural stem cells selectively travel to tumor cells. Karen Aboody, M.D., has begun groundbreaking research in discovering and exploiting this finding, allowing her to use neural stem cells to selectively deliver therapeutic agents to target tumor cells in the brain. The neural stem cells are genetically modified to produce therapeutic gene products, which effectively infiltrate and kill brain tumor cells.
Principal investigator: Karen Aboody, M.D.
 
Finding Better Treatments for Brain Tumors

Cancers that originate in the brain, termed primary brain tumors, are among the most difficult to treat. The effectiveness of chemotherapy is often hindered by the presence of the blood brain barrier, which prevents most drugs from getting into the brain. Traditional chemotherapy tends to kill both cancer cells and normal cells, often resulting in undesired side effects.
City of Hope researchers are studying ways to target only the brain tumor while limiting damage to normal brain tissue using neural stem cells (NSCs) to deliver anti-cancer treatment directly to tumor cells. NSCs hold the promise of improved treatment for brain cancers because they have a natural ability to seek out and distribute themselves within a tumor, as well as track to other sites of tumor in the brain. Because they can find tumor cells, NSCs may offer a new way to bring more chemotherapy directly to brain tumors. After modifying the NSCs by transferring a therapeutic gene into them, NSCs can serve as vehicles to deliver anti-cancer treatment directly to the primary tumor, as well as potentially to target malignant cells that have spread away from the original tumor site.
Principal investigator: Jana Portnow, M.D.
 
Caption: Neural Stem Cells (NSCs) have a natural tendency to migrate to tumor cells. The orally given inactive drug (prodrug) crosses the blood brain barrier and is converted into a chemotherapeutic agent within the NSC. The agent is then released from the NSC to selectively destroy dividing tumor cells. This strategy has a large ‘bystander effect’ thereby resulting in destroying many surrounding tumor cells with just one NSC.
 
 
GENE THERAPY
 
Creating an Innovative Approach to Therapy

Macrophages are plentiful around tumor sites; however, they aid tumor growth instead of mounting an immune attack.  Behnam Badie, M.D., has found that these tumor-associated macrophages express high levels of an enzyme that inhibits the attack of T cells, the next line of immune response, and he has devised a pioneering concept to use tumor-associated macrophages to deliver genetic material to tumors.
 
The first step is a bone marrow transplant to remove the patient’s existing immune system and replace it with white blood cells that give rise to new modified macrophages. These macrophages are engineered with an inactive gene, which needs a promoter to become active. The modified macrophage will still respond to the tumor’s manipulation by traveling to the tumor site and secreting proteins that stimulate tumor growth. These proteins are the “promoters” that activate the genetic material.
 
At the same time, the patient is administered a prodrug, which is inactive. The activated gene makes material that converts the prodrug into active chemotherapy — which kills tumor cells. Meanwhile, that same active genetic material induces suicide in macrophages, so that they can no longer be employed for tumor growth. And because these modified macrophages are born from the new white blood cells, if the tumor reappears, the new macrophages will halt new tumor growth.
Principal Investigator: Behnam Badie, M.D.
 
 
Gene Therapy for Metastatic Brain Tumors

Despite advances in surgical techniques and the use of radiotherapy and chemotherapy, metastatic brain tumor still remains a disease of high mortality; therefore alternative treatments warrant further investigation. Gene therapy is one such alternative treatment, and is based upon understanding the disease at a molecular level.
 
Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person’s cells to fight disease. The purpose of cancer gene therapy is to eliminate tumor cells while sparing non-tumor cells from the cytotoxic (cell-killing) effects of the cancer treatment. In general, a gene cannot be directly inserted into a person’s cell. It must be delivered to the cell using a carrier, or “vector.” The vectors most commonly used in gene therapy are viruses.
 
Researchers are exploring adeno-associate virus (AAV) as a gene therapy vector because of a number of positive attributes:
  • AAV appears to be non-pathogenic (the virus doesn’t cause disease).
  • It can easily infect most cells.
  • It stably integrates into the host cell DNA at a specific site without causing harmful mutations.
  • It causes very little immune response.
 
Given the above, we propose inserting a suicide gene, which is only expressed in metastatic brain tumors but not in normal cells, into the AAV virus vector. The virus, bearing the suicide gene, then infects cells; however, only metastatic brain tumor cells are affected by the cancer-killing suicide gene protein. This extraordinary approach should provide the selectivity necessary to treat this challenging disease.
Principal investigators: Michael Y. Chen, M.D., Ph.D. , and Rahul Jandial, M.D., Ph.D.
 
 
Convection-enhanced Delivery

Michael Y. Chen, M.D., is studying a gene therapy approach that makes use of the basic biological difference between normal brain tissue and cancer tissue. Tyrosinase promoter is a cellular switch that is highly functional in cancer tissue while inactive in normal brain tissue. The saporin protein is a compound that acts on the “switch” activity, such as the tyrosinase promoter, and converts itself into a therapeutic agent. Dr. Chen’s research team intends to use the tyrosinase promoter as a switch to control the expression of the therapeutic agent saporin that will limit destruction to only cancer cells. The saporin gene will be introduced into a viral gene therapy vector and implanted into the tumor via Convection-enhanced Delivery (CED). CED is the process of continued injection under increased pressure of a fluid containing a therapeutic agent.
Principal investigator: Michael Y. Chen, M.D., Ph.D.
 
 
MINIMALLY INVASIVE APPROACHES
 
Designing Leading-Edge Technology for Delivering Targeted Treatment

Behnam Badie, M.D., has designed a minimally invasive technique to debulk and treat brain tumors without open surgery – making treatment more effective while reducing trauma, the amount of drug used and time involved. The technique involves Badie inserting into the tumor a narrow cylinder, through which a small instrument reaches in and debulks it. The result is a reservoir in the center of the tumor into which a small tube is inserted and left just under the scalp to inject large amounts of targeted therapy.
Principal investigator: Behnam Badie, M.D.
 
 
CHEMOTHERAPY

Uncovering New Targets for Treatment

Macrophages are a first line of immune defense. They detect foreign debris, like bacteria and viruses, and present the proteins from these invaders to T cells, another type of immune cell that then mounts a coordinated attack. Brain tumor cells evade this response and more – they manipulate macrophages to work for them by supplying the tumor with oxygen and nutrients. Macrophages found around tumor cells also secrete proteins that encourage tumor cell growth.
 
Behnam Badie, M.D., and his team are researching new therapies to fight or reverse this manipulated response. They have found a protein secreted by tumor cells called S100B, which they believe plays a feature role in cancer’s ability to attract and subvert macrophages, and they are now working with City of Hope’s High Throughput Screening Core to identify lead compounds that inhibit S100B.
Principal investigator: Behnam Badie, M.D.

Microdialysis Catheter

Delivering substances to the brain has long been a barrier to effective treatment of brain tumors. New targeted therapies that can cross the blood-brain barrier offer promising treatment options. However, difficulties in determining whether these agents can attain therapeutic levels within the brain hinder their screening and evaluation.
 
To determine how chemotherapy drugs perform within the brain, City of Hope researchers are implanting eligible brain tumor patients who volunteer for the study with a microdialysis catheter, which is a temporary small tube that has a semi-permeable membrane at the tip. Through this tube, they can sample the fluid in the brain to measure concentrations of chemotherapy. The results will help reveal how drugs work to fight cancer cells in real time, leading to more effective treatments in the future.
 
 
If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about  becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.

Living with Brain Tumors

While our primary goal is to cure or control the disease, another top priority is relieving suffering and discomfort for brain tumors patients undergoing treatments.
 
In addition to curative treatments, City of Hope brain tumor patients and their caregivers have access to the broad range of services offered by our Department of Supportive Care Medicine. The department’s staff of professionals, including supportive medicine physicians, rehabilitation therapists, psychiatrists, support groups and clinical social workers, can help patients and loved ones with a variety of care and wellness issues including:

  • Managing cancer or treatment effects such as pain, nausea and fatigue
  • Palliative care to reduce discomfort and stress, physical and mental, throughout diagnosis and treatment
  • Maintaining and restoring cognitive function
  • Adjusting to new dietary and lifestyle habit changes during and following treatment
  • Coping and maintaining emotional/social/spiritual well-being
  • Navigating through the health care system
  • Staying healthy and active during/after treatment
  • Healing arts
  • Building caregivers’ skills
 
The Department of Supportive Care Medicine is based in City of Hope’s Sheri & Les Biller Patient and Family Resource Center, which integrates all support services in a central location. The Biller Resource Center provides a warm and welcoming space where patients, families and caregivers can access the resources, education and support they need to strengthen and empower themselves, before, during and after treatment.
 
For more information or to contact the Biller Resource Center staff, please call 626-256-4673, ext. 32273 (3CARE).
 
 
This site includes tips, tools and online resources to help cancer patients and their families with issues that arise during cancer treatment.

Additional Resources

 
 
If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about  becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.
 

Support this program

We deliver exquisite care at the leading edge of cancer treatment. It takes the help of a lot of caring people to make hope a reality for our patients. City of Hope was founded by individuals' philanthropic efforts over 100 years ago. Their efforts - and those of our supporters today - have built the foundation for the care we provide and the research we conduct. It enables City of Hope to strive for new breakthroughs and better therapies - helping more people enjoy longer, better lives.

For more information on supporting this specific program, please contact:

Julie Hara

Senior Development Officer
Phone: 626-218-0869
Email: juhara@coh.org

 
 

Brain Tumors

Brain Tumor Program

City of Hope is a leader in the diagnosis, treatment and research of brain cancers and tumors. Our specialized brain tumor program takes a comprehensive, patient-centered approach to treating a broad variety of tumors, including:
 
  • Gliomas
    • Astrocytomas
    • Oligodendrogliomas
    • Ependymomas
    • Mixed gliomas
    • Glioblastoma multiforme
  • Meningiomas
  • Medulloblastomas
  • Schwannomas
  • Craniopharyngiomas
  • Secondary brain tumors (metastases from other cancers)
  • Benign tumors in the brain and surrounding tissues (such as the pituitary gland )
 
Our multidisciplinary team of health care professionals take an integrated approach to treating this disease by combining the latest research findings with outstanding patient care. This includes using advanced technologies and specialized techniques such as:
 
  • minimally-invasive surgical techniques minimally-invasive surgical techniques that can remove the tumor with less impact to the surrounding healthy brain tissue; our neurosurgeons’ expertise in biopsy and resection also means they can access and treat brain tumors that are considered inoperable elsewhere
  • Tumor Treating Fields therapy, which uses an alternating, low current electric field to block and reverse brain tumor growth by interfering with tumor cell division
  • highly precise radiation therapy  that can target tumor sites with minimal exposure to nearby tissues
  • targeted drugs and drug combinations that can treat hi-grade tumor with greater effectiveness and fewer side effects
 

New Clinical Study for Recurrent Glioblastoma Being Conducted at City of Hope

Neural Stem Cells (NSCs) have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
IRB# 13401: A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified NSCs. These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU. The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please call 626-471-9393 or email at neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 

 
Additionally, City of Hope patients have access to our extensive team of supportive care experts — including rehabilitation specialists, palliative care physicians and clinical social workers. Working closely with the patient’s primary care team, they can detect and address quality of life issues related to brain tumor diagnosis and treatments. This includes  managing symptoms (such as nausea, fatigue and cognitive effects), maintaining quality of life throughout treatment and adjusting to a post-treatment lifestyle.
 
Learn more about brain tumor types, symptoms, risk factors and diagnostic tests on National Cancer Institute’s website.
 
 
 
As one of a handful of institutes to attain the elite designation of Comprehensive Cancer Center by the National Cancer Institute, City of Hope is acknowledged as a leader in research and treatment of brain tumors. With our decades of experience, specialized therapy protocols and extensive program of clinical trials, newly diagnosed or relapsed patients can find a treatment regimen that is tailored to their needs and gives them the best chance for survival. U.S. News & World Report also named City of Hope as one of the top cancer hospitals in the country.
 
 
If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about  becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.
 
 
 
 
 

Brain Tumor Team

Brain Tumor Team

Our Treatment Approach

Our Treatment Approach to Brain Tumors

City of Hope has one of the most renowned brain tumor programs in the United States, with a multidisciplinary team of medical experts across different fields including surgery, radiation oncology, medical oncology and supportive care medicine. Together, they work collaboratively to plan and implement a treatment regimen that is individually tailored to the patient to improve survival chances, enhance outcomes, minimize side effects and boost quality of life.

Surgery

For operable brain tumors, surgical removal of the cancer is typically the first treatment provided and can be curative for early stage patients. However, it is also a viable option for patients with advanced or high-grade tumors, significantly improving outcomes and quality of life. Our neurosurgery team’s focus on researching and treating brain tumors also means they can target tumors that are considered inoperable elsewhere.
 
City of Hope’s neurosurgeons also specialize in minimally invasive procedures whenever possible. By using fewer incisions and making smaller cuts, our surgeons can remove and extract the tumor with minimal impact to the surrounding healthy brain tissue. As a result, patients experience less discomfort, fewer post-surgical complications and a faster recovery time.
 
These procedures include:
 
  • Intraoperative cortical mapping: This technology gives the surgeon a computerized map of key brain regions, including speech, motor and sensory centers. By avoiding these critical areas, the risk of neurological damage is minimized while allowing as much of the tumor to be removed as possible.   
  • Image-guided surgical navigation: This technology helps guide the removal of tumors that are difficult to visualize or are located in “high-risk” areas of the brain by using preoperative magnetic resonance images (MRIs).
  • Endoscopic surgery: Certain brain surgery procedures may be performed through an endoscope - a thin, lighted tube that requires a small opening and accommodates tiny surgical tools. Smaller openings minimize postoperative discomfort and risk of infection. City of Hope researchers are working to develop a miniaturized surgical system that will allow brain surgeries to be even less invasive, with an even lower risk of complications.
 
Our neurosurgeons also work closely with radiation and medical oncologists so that multiple treatments can be performed in one procedure. For example, after resection they can apply chemotherapy directly to the surgery site, which can kill remaining tumor cells and reduce the likelihood of recurrence.
 

Radiation Therapy

For some brain tumors — particularly those that cannot be treated with surgery — radiation can target and kill brain tumor cells, improving survival outcomes and providing symptom relief.
Radiation may also be performed after surgery to kill any remaining abnormal cells at the tumor site, or combined with chemotherapy to improve the effectiveness of both therapies.
 
In addition to standard radiation regimens, City of Hope also offers Helical TomoTherapy, an advance technology combining radiation delivery with advanced imaging. This allows the radiation beams to be “sculpted” to the tumor’s size and shape, resulting in more focused radiation on the cancer site while minimizing exposure to adjacent tissues and organs. This can reduce the likelihood and severity of side effects, as well as preserving cognitive function.
 

Alternating Electric Field Therapy

Brain tumor patients at City of Hope may be treated by the recently approved alternating electric field therapy (also known as tumor treating fields or TTF.) This treatment targets and attacks tumor cells through an alternating, low-intensity electrical field, blocking tumor cell division processes.
 
The therapy is non-invasive (the current-producing transducers are placed directly on the skin around the tumor region) and is portable, allowing patients to be continuously treated while they go about their normal activities throughout the day.

Drug Therapy

City of Hope uses a wide range of chemotherapy, targeted therapy and immunotherapy drugs to treat brain tumors. These drugs may be taken orally, intravenously (injected into the bloodstream) or applied directly at the tumor site during surgery.
 
In addition to standard drug regimens, patients have access to newly developed drugs (or drug combinations) through our clinical trials program.
 
These drugs can also enhance the effectiveness of other brain tumor treatments by shrinking the tumor beforehand — making it easier to extract with surgery or target with radiation — or lowering chances of recurrence afterwards by targeting and attacking any remaining tumor cells.
 
As part of the treatment team, a medical oncologist will evaluate the patient’s cancer, health and other factors, so that the drug therapy regimen can be tailored to the patient throughout the continuum of care.
 

Become a Patient

If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.

Clinical Trials

Brain Tumor Clinical Trials

City of Hope currently has many clinical trials in progress, a number of which address malignant brain tumors. Clinical trials offer patients new and promising experimental treatments not available elsewhere. In fact, nearly one in two patients at City of Hope is part of a clinical trial. These trials evaluate the safety and efficacy of prospective therapies. Participants in clinical trials receive excellent care and are closely monitored. We encourage all brain tumor patients to participate in clinical trials since that will enable us to find better treatments for brain tumors.
 
 
For more information about the studies listed below including eligibility criteria, please call: 626-471-9393. For a summary of these studies including eligibility criteria, visit the City of Hope clinical trials website.
 
Newly Diagnosed
 
11180  
A Phase III Clinical Trial Evaluating DCVax®-Brain, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma
                                                                                                                                   
Recurrent Disease
 
13401
A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
Neural Stem Cells have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified neural stem cells (NSCs).  These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU.  The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please call 626-471-9393 or email neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 
13116
A Phase I Gene Therapy Trial of the Safety and Tolerability of Toca 511 in patients Recurrent High Grade Glioma
 
LEARN MORE ABOUT THE TOCA 511 & TOCA FC STUDIES
TOCA 511 & TOCA FC mechanism
This is a very exciting new experimental gene therapy treatment for high grade brain tumors. The basic concept is that a virus (Toca 511) is injected into the tumor. This virus was designed to infect only the brain tumor cells and leave the normal cells alone. When it infects a cell, it adds a gene to the cell which encodes for an enzyme that can convert an antibiotic drug (Toca FC) into a toxic chemotherapy (5-FU), selectively in the tumor. This drug (Toca FC) is given orally every few weeks, and it kills the tumor cells that have enough copies of this enzyme to convert Toca FC to 5-FU. The tumor cells that are infected but don't have enough of the enzyme act as a reservoir - they start the process over again - spreading the infection for a few more weeks, and these cycles are repeated over and over again until the entire tumor is potentially gone.
 
If you were diagnosed with Recurrent High Grade Glioma (HGG) (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma) that have increased in size following treatment with surgery, radiation therapy and temozolomide. The Toca 511 and Toca FC studies might be the studies for you.
 
Who can participate in the Toca 511 & Toca FC studies? You may qualify for a Toca 511 & Toca FC study if you:
 
  • Are at least 18 years old (upper limit of 80 years in one of the studies)
  • Have recurrent HGG
     
Your doctor will be able to review with you these and other eligibility criteria. For more information about the Toca 511 & Toca FC studies, please contact Jana Portnow M.D. or Behnam Badie M.D. at  626-471-9393 or visit www.tocagen.com.
 
Non-Therapeutic
 
11320
Feasibility of Intraoperative Optical Imaging and Spectroscopy in Brain Tumors
 
13459
Phase 2, Open-Label, Imaging Trial of I-124-CLR1404 in Patients with Newly Diagnosed or Recurrent Glioblastoma Multiforme. (CELLECTAR)

Research

Brain Tumor Research


There is extensive collaboration between City of Hope clinicians and researchers to develop and evaluate new cancer therapies designed to improve survival and quality of life outcomes. City of Hope patients have access to a wide variety of clinical trials ranging from new chemotherapy and targeted therapies, novel surgical techniques, new radiation approaches and strategies to minimize side effects and chances of cancer recurrence.
 
Our current brain tumor research efforts include:
 
IMMUNOTHERAPY

Unlike drugs that act by chemically killing cancer cells or halting their growth, immunotherapy uses the body’s own immune system to trigger its ability to seek out and kill cancer. City of Hope scientists are working on several immunotherapy approaches designed to exploit the body’s natural defenses against the disease:

Nanotubes: Small and Lethal Envelopes Used to Kill Cancer

Nanotubes are microscopic technology shaped into tiny tubes about 1/10,000th the width of a human hair.  Behnam Badie, M.D., is working closely with Jacob Berlin, Ph.D., to use nanotubes to deliver a drug called CpG, which activates immune cells called macrophages to recognize and attack tumor cells. Because nanotubes can carry the drug directly to macrophages around the tumor, patients can receive stronger dosages, tolerate their therapy better and recover more quickly.
Principal investigators: Behnam Badie, M.D.; Jacob Berlin, Ph.D. and Leying (Larry) Zhang, Ph.D.
 
 
Nanoparticles: Guiding Cancer Treatment to the Tumor with Magnets

Behnam Badie, M.D., is collaborating with scientists at Caltech to design a dynamically programmable, low-intensity magnetic field to route and traffic macrophages that have been treated with CpG to tumor sites. In this method, patients would receive CpG-loaded nanoparticles engineered with an iron oxide, so that the macrophages become magnetic.  The magnetic field is generated by a grid, which allows for control over the spatial and temporal profile. Dr. Badie believes that directing CpG-treated macrophages to the areas where they are needed will make this treatment approach even more effective and durable.
Principal investigator: Behnam Badie, M.D.
 
Macrophages and Microglia: Harnessing the Immune System's Clean-up Crew

Macrophages are immune cells that act as scavengers feeding upon dead cells, foreign substances, and other debris in the body. Microglia are macrophages specific to the central nervous system. Microglia are normally inactive but become activated in response to inflammation, infection and trauma. Once activated, they proliferate and migrate to the site of injury. Behnam Badie, M.D., is researching ways to improve outcomes in post-surgical brain tumor patients by re-engineering the microglia to deliver therapeutic agents to the tumor site, killing residual tumor cells. He also aims to extend the life of T cells using microglia and test their efficacy against cancer. This study will likely garner results within a year, setting the stage for Phase I clinical trials.
Principal investigators: Behnam Badie, M.D. , and Leying (Larry) Zhang, Ph.D.
 
T cells: Maximizing a Patient's Immune System

The Cellular Immunotherapy program, led by Stephen J. Forman, M.D., F.A.C.P. , chair, Hematology & Hematopoietic Cell Transplantation, continues to develop innovative treatments that reduce the need for harsh radiation and chemotherapy. One of the most exciting programs underway at City of Hope, the cellular immunotherapy program is developing technology to take T cells from a cancer patient and reprogram them through genetic engineering to target and eradicate the patient’s cancer.
 
Using pioneering technology, we have been able to isolate immune cells from a patient’s blood sample and then engineer those cells to express an artificial receptor that will seek out and attack cancer cells. In the lab, our researchers then grow billions of identical, reprogrammed T cells. In the clinic, the T cells are re-infused into the patient, where they go to work eliminating the cancer. Under Forman’s leadership, City of Hope has conducted the first-ever FDA-authorized clinical trials using reprogrammed T cell therapy for lymphoma, neuroblastoma and glioma.
 
In the glioma study currently underway, patients are infused with engineered T cells that respond to an antigen called CD8. An antigen is any foreign substance to which the body reacts by dispatching antibodies such as T cells. These reprogrammed T cells act as homing devices to take the body’s T cells to the cancer. Although only glioma patients were initially targeted for treatment, researchers have plans to expand this therapy to another brain tumor, medulloblastoma, in pediatric patients.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 2 T cells: Universal T cells

One prong of research seeks to formulate a T cell that is protected from rejection by the patient’s own immune system, thus becoming a potential “universal T cell” for patients everywhere. Specifically, Generation 2 T cells are programmed to be accepted without triggering a rejection reaction. By developing such a T cell, our researchers thus create a means to mass produce T cells from one patient on behalf of thousands more. The first glioma patient treated with Generation 2 T cells was in 2007 — the first in the world to be treated with this novel therapy.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 3 T-cells: Stacking the Deck Against Cancer

While City of Hope researchers develop the autoimmune-resistant T cell, they plan to adapt it to create Generation 3 T cells. The goal is to develop technology that enables researchers to equip Generation 2 T cells with additional cancer-fighting therapeutic material to strengthen their impact against cancer. John Rossi, Ph.D., chairman and professor of Molecular Biology at City of Hope, and Forman are using interfering ribonucleic acid (RNAi) inside T cells to make them even more effective cancer combatants. A drug using RNAi is set for clinical trials.
Principal investigators: Stephen J. Forman, M.D., F.A.C.P. , and John Rossi, Ph.D.
 
 
STEM CELL THERAPY
 
Neural Stem Cells: One-Way Tickets to Tumors

Neural stem cells selectively travel to tumor cells. Karen Aboody, M.D., has begun groundbreaking research in discovering and exploiting this finding, allowing her to use neural stem cells to selectively deliver therapeutic agents to target tumor cells in the brain. The neural stem cells are genetically modified to produce therapeutic gene products, which effectively infiltrate and kill brain tumor cells.
Principal investigator: Karen Aboody, M.D.
 
Finding Better Treatments for Brain Tumors

Cancers that originate in the brain, termed primary brain tumors, are among the most difficult to treat. The effectiveness of chemotherapy is often hindered by the presence of the blood brain barrier, which prevents most drugs from getting into the brain. Traditional chemotherapy tends to kill both cancer cells and normal cells, often resulting in undesired side effects.
City of Hope researchers are studying ways to target only the brain tumor while limiting damage to normal brain tissue using neural stem cells (NSCs) to deliver anti-cancer treatment directly to tumor cells. NSCs hold the promise of improved treatment for brain cancers because they have a natural ability to seek out and distribute themselves within a tumor, as well as track to other sites of tumor in the brain. Because they can find tumor cells, NSCs may offer a new way to bring more chemotherapy directly to brain tumors. After modifying the NSCs by transferring a therapeutic gene into them, NSCs can serve as vehicles to deliver anti-cancer treatment directly to the primary tumor, as well as potentially to target malignant cells that have spread away from the original tumor site.
Principal investigator: Jana Portnow, M.D.
 
Caption: Neural Stem Cells (NSCs) have a natural tendency to migrate to tumor cells. The orally given inactive drug (prodrug) crosses the blood brain barrier and is converted into a chemotherapeutic agent within the NSC. The agent is then released from the NSC to selectively destroy dividing tumor cells. This strategy has a large ‘bystander effect’ thereby resulting in destroying many surrounding tumor cells with just one NSC.
 
 
GENE THERAPY
 
Creating an Innovative Approach to Therapy

Macrophages are plentiful around tumor sites; however, they aid tumor growth instead of mounting an immune attack.  Behnam Badie, M.D., has found that these tumor-associated macrophages express high levels of an enzyme that inhibits the attack of T cells, the next line of immune response, and he has devised a pioneering concept to use tumor-associated macrophages to deliver genetic material to tumors.
 
The first step is a bone marrow transplant to remove the patient’s existing immune system and replace it with white blood cells that give rise to new modified macrophages. These macrophages are engineered with an inactive gene, which needs a promoter to become active. The modified macrophage will still respond to the tumor’s manipulation by traveling to the tumor site and secreting proteins that stimulate tumor growth. These proteins are the “promoters” that activate the genetic material.
 
At the same time, the patient is administered a prodrug, which is inactive. The activated gene makes material that converts the prodrug into active chemotherapy — which kills tumor cells. Meanwhile, that same active genetic material induces suicide in macrophages, so that they can no longer be employed for tumor growth. And because these modified macrophages are born from the new white blood cells, if the tumor reappears, the new macrophages will halt new tumor growth.
Principal Investigator: Behnam Badie, M.D.
 
 
Gene Therapy for Metastatic Brain Tumors

Despite advances in surgical techniques and the use of radiotherapy and chemotherapy, metastatic brain tumor still remains a disease of high mortality; therefore alternative treatments warrant further investigation. Gene therapy is one such alternative treatment, and is based upon understanding the disease at a molecular level.
 
Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person’s cells to fight disease. The purpose of cancer gene therapy is to eliminate tumor cells while sparing non-tumor cells from the cytotoxic (cell-killing) effects of the cancer treatment. In general, a gene cannot be directly inserted into a person’s cell. It must be delivered to the cell using a carrier, or “vector.” The vectors most commonly used in gene therapy are viruses.
 
Researchers are exploring adeno-associate virus (AAV) as a gene therapy vector because of a number of positive attributes:
  • AAV appears to be non-pathogenic (the virus doesn’t cause disease).
  • It can easily infect most cells.
  • It stably integrates into the host cell DNA at a specific site without causing harmful mutations.
  • It causes very little immune response.
 
Given the above, we propose inserting a suicide gene, which is only expressed in metastatic brain tumors but not in normal cells, into the AAV virus vector. The virus, bearing the suicide gene, then infects cells; however, only metastatic brain tumor cells are affected by the cancer-killing suicide gene protein. This extraordinary approach should provide the selectivity necessary to treat this challenging disease.
Principal investigators: Michael Y. Chen, M.D., Ph.D. , and Rahul Jandial, M.D., Ph.D.
 
 
Convection-enhanced Delivery

Michael Y. Chen, M.D., is studying a gene therapy approach that makes use of the basic biological difference between normal brain tissue and cancer tissue. Tyrosinase promoter is a cellular switch that is highly functional in cancer tissue while inactive in normal brain tissue. The saporin protein is a compound that acts on the “switch” activity, such as the tyrosinase promoter, and converts itself into a therapeutic agent. Dr. Chen’s research team intends to use the tyrosinase promoter as a switch to control the expression of the therapeutic agent saporin that will limit destruction to only cancer cells. The saporin gene will be introduced into a viral gene therapy vector and implanted into the tumor via Convection-enhanced Delivery (CED). CED is the process of continued injection under increased pressure of a fluid containing a therapeutic agent.
Principal investigator: Michael Y. Chen, M.D., Ph.D.
 
 
MINIMALLY INVASIVE APPROACHES
 
Designing Leading-Edge Technology for Delivering Targeted Treatment

Behnam Badie, M.D., has designed a minimally invasive technique to debulk and treat brain tumors without open surgery – making treatment more effective while reducing trauma, the amount of drug used and time involved. The technique involves Badie inserting into the tumor a narrow cylinder, through which a small instrument reaches in and debulks it. The result is a reservoir in the center of the tumor into which a small tube is inserted and left just under the scalp to inject large amounts of targeted therapy.
Principal investigator: Behnam Badie, M.D.
 
 
CHEMOTHERAPY

Uncovering New Targets for Treatment

Macrophages are a first line of immune defense. They detect foreign debris, like bacteria and viruses, and present the proteins from these invaders to T cells, another type of immune cell that then mounts a coordinated attack. Brain tumor cells evade this response and more – they manipulate macrophages to work for them by supplying the tumor with oxygen and nutrients. Macrophages found around tumor cells also secrete proteins that encourage tumor cell growth.
 
Behnam Badie, M.D., and his team are researching new therapies to fight or reverse this manipulated response. They have found a protein secreted by tumor cells called S100B, which they believe plays a feature role in cancer’s ability to attract and subvert macrophages, and they are now working with City of Hope’s High Throughput Screening Core to identify lead compounds that inhibit S100B.
Principal investigator: Behnam Badie, M.D.

Microdialysis Catheter

Delivering substances to the brain has long been a barrier to effective treatment of brain tumors. New targeted therapies that can cross the blood-brain barrier offer promising treatment options. However, difficulties in determining whether these agents can attain therapeutic levels within the brain hinder their screening and evaluation.
 
To determine how chemotherapy drugs perform within the brain, City of Hope researchers are implanting eligible brain tumor patients who volunteer for the study with a microdialysis catheter, which is a temporary small tube that has a semi-permeable membrane at the tip. Through this tube, they can sample the fluid in the brain to measure concentrations of chemotherapy. The results will help reveal how drugs work to fight cancer cells in real time, leading to more effective treatments in the future.
 
 
If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about  becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.

Living with Brain Tumors

Living with Brain Tumors

While our primary goal is to cure or control the disease, another top priority is relieving suffering and discomfort for brain tumors patients undergoing treatments.
 
In addition to curative treatments, City of Hope brain tumor patients and their caregivers have access to the broad range of services offered by our Department of Supportive Care Medicine. The department’s staff of professionals, including supportive medicine physicians, rehabilitation therapists, psychiatrists, support groups and clinical social workers, can help patients and loved ones with a variety of care and wellness issues including:

  • Managing cancer or treatment effects such as pain, nausea and fatigue
  • Palliative care to reduce discomfort and stress, physical and mental, throughout diagnosis and treatment
  • Maintaining and restoring cognitive function
  • Adjusting to new dietary and lifestyle habit changes during and following treatment
  • Coping and maintaining emotional/social/spiritual well-being
  • Navigating through the health care system
  • Staying healthy and active during/after treatment
  • Healing arts
  • Building caregivers’ skills
 
The Department of Supportive Care Medicine is based in City of Hope’s Sheri & Les Biller Patient and Family Resource Center, which integrates all support services in a central location. The Biller Resource Center provides a warm and welcoming space where patients, families and caregivers can access the resources, education and support they need to strengthen and empower themselves, before, during and after treatment.
 
For more information or to contact the Biller Resource Center staff, please call 626-256-4673, ext. 32273 (3CARE).
 
 
This site includes tips, tools and online resources to help cancer patients and their families with issues that arise during cancer treatment.

Additional Resources

 
 
If you have been diagnosed with a brain tumor or are looking for a second opinion consultation about your treatment, find out more about  becoming a patient by calling 800-826-HOPE or filling out the Request a New Patient Appointment Online form.
 

Support This Program

Support this program

We deliver exquisite care at the leading edge of cancer treatment. It takes the help of a lot of caring people to make hope a reality for our patients. City of Hope was founded by individuals' philanthropic efforts over 100 years ago. Their efforts - and those of our supporters today - have built the foundation for the care we provide and the research we conduct. It enables City of Hope to strive for new breakthroughs and better therapies - helping more people enjoy longer, better lives.

For more information on supporting this specific program, please contact:

Julie Hara

Senior Development Officer
Phone: 626-218-0869
Email: juhara@coh.org

 
 
Quick Links
Featured Videos
Division of Neurosurgery
City of Hope has some of the most advanced tools for the surgical removal of brain and spine tumors. Learn how these tools have enabled surgery of the highest precision while minimizing adverse outcomes.
 
City of Hope’s Division of Neurosurgery focuses on surgical treatment of both benign and malignant brain, spine and pituitary tumors. Our physicians are nationally-recognized experts in neurosurgery and neuro-oncology, and employ today’s leading edge therapies.

For questions or additional information, please call 626-471-7100.
Brain Tumor Medical Minute
Refer a Patient
Physicians can choose a number of options to refer a patient:

 


NEWS & UPDATES
  • Urinary tract stones are hard masses, or calculi, that form in the urinary tract and may cause pain, bleeding or an infection, or even block of the flow of urine. Urinary tract stones begin to form in a kidney and may enlarge in a ureter or the bladder. Depending on where a stone is located, […]
  • Every summer, hospitals nationwide experience a shortage of blood donations. This summer is no exception. Nearly 1.7 million new cancer cases are expected to be diagnosed in the U.S. this year,  and many of those patients will need blood transfusions during their treatment. Patients at City of Hope alone rely o...
  • Non-Hodgkin lymphoma facts: Non-Hodgkin lymphoma is a cancer that starts in cells called lymphocytes, which are part of the body’s immune system. Lymphocytes are in the lymph nodes and other lymphoid tissues (such as the spleen and bone marrow). Non-Hodgkin lymphoma is one of the most common cancers in the U.S....
  • Few clinical cancer trials include older adults – and yet, more than 60 percent of cancer cases in the United States occur in people age 65 and older. The result is a dearth of knowledge on how to treat the very population most likely to be diagnosed with cancer. Now, the American Society of Clinical […]
  • Scientists at City of Hope and UCLA have become the first to inhibit the expression of a protein, called TWIST that promotes tumor invasion and metastasis when activated by cancer cells. As such, they’ve taken the first step in developing a potential new therapy for some of the deadliest cancers, including ovar...
  • Upon completing her final round of chemotherapy for ovarian cancer earlier this month, Maria Velazquez-McIntyre, a 51-year-old Antelope Valley resident, celebrated the milestone by giving other patients a symbol of hope – a Survivor Bell. The bell may look ordinary, but for cancer patients undergoing chemothera...
  • Many Americans understand that obesity is tied to heart disease and diabetes but, according to a new survey, too few – only 7 percent – know that obesity increases the risk of cancer. Specific biological characteristics can increase cancer risk in obese people, and multiple studies have shown correlations betwe...
  • As breast cancer survivors know, the disease’s impact lingers in ways both big and small long after treatment has ended. A new study suggests that weight gain – and a possible corresponding increase in heart disease and diabetes risk – may be part of that impact. In the first study to evaluate weight chan...
  • Becoming what’s known as an independent scientific researcher is no small task, especially when working to translate research into meaningful health outcomes. Yet that independent status is vital, enabling researchers to lead studies and avenues of inquiry that they believe to be promising. Clinicians, especial...
  • 720 days. That’s how long Alex Tung, 38, had to give up surfing after being diagnosed with acute myeloid leukemia. For most people, even some surfers, such a hiatus wouldn’t be a big deal, but for Tung, surfing has been everything. The Southern California resident began surfing when he was in elemen...
  • There are few among us who have not experienced loss of a friend or loved one, often without warning, or like those of us who care for people with cancer, after a lingering illness. It is a time when emotions run high and deep, and as time passes from the moment of loss, we often […]
  • For the past four years, neurosurgeon and scientist Rahul Jandial, M.D., Ph.D., has been studying how breast cancer cells spread, or metastasize, to the brain, where they become life-threatening tumors. Known as secondary brain tumors, these cancers have become increasingly common as treatment advances have ena...
  • Cutaneous T cell lymphomas are types of non-Hodgkin lymphoma that arise when infection-fighting white blood cells in the lymphatic system – called lymphocytes – become malignant and affect the skin. A primary symptom is a rash that arises initially in areas of the skin that are not normally exposed to sunlight....
  • There’s science camp, and then there’s “mystery” science camp. City of Hope’s new science camp for middle school students is of the especially engaging latter variety. From Monday, July 13, to Friday, July 17, rising middle-school students from across the San Gabriel Valley were presented with a “patient” with ...
  • Women diagnosed with breast cancer quickly learn their tumor’s type, meaning the characteristics that fuel its growth. That label guides the treatment of their disease, as well as their prognosis when it comes to treatment effectiveness. Sometimes, however, doctors can’t accurately predict treatment effectivene...