Research is vitally important for finding and providing new or improved treatments. Money for research is very limited. The number of diagnosed cases of medulloblastoma is quite small compared to other forms of cancer and therefore does not receive adequate funding. While this is understandable, it demonstrates the importance of funding research. Current research is being carried out to determine the biology of the tumor, its cell origin, and what controls its growth. By understanding the biology of the tumor, the goal of finding a cure can be achieved. Research is also being performed to find ways to make treatments safer for children, so that they not only survive, but experience a good quality of life.
Current Medulloblastoma Research
St. Jude finds signaling system that halts the growth of a childhood brain cancer (news release) Memphis, Tennessee, March 14, 2008
A discovery by St. Jude Children’s Research Hospital scientists suggests a safer way to treat medulloblastoma, a rare but often fatal childhood brain tumor. The group found that one of the brain’s signaling pathways inhibits the growth of the highly aggressive cancer cells. The researchers discovered that three proteins, designated BMP2, BMP4 and BMP7, halted the growth of medulloblastoma tumors and induced the malignant cells to develop into normal neurons.
Key medulloblastoma brain cancer genes pinpointed March 2009
Scientists at St. Jude have generated new models of medulloblastoma tumors by inactivating different DNA repair pathways, specifically in the brain. Investigators found that in all medulloblastomas a gene called Patched 1 (Ptch1) was inactivated, showing that this gene plays an important role in medulloblastoma. The approach offers promise for understanding other types of brain tumors and developing new treatments for these cancers.
What is the role of proton therapy in the treatment of children with medulloblastoma? August 25, 2010
It provides precise treatment with fewer late effects. The major advantage of proton therapy is being able to direct the beam and have it stop where you want it to stop. In medulloblastoma, we must treat the cerebral spinal fluid pathway, the whole brain and the whole spine, to a certain dose based on the patient’s level of risk, followed by a boost to the primary area.
Roche drug combats children’s brain tumors Sat Jun 5, 2010 CHICAGO (Reuters)
An experimental drug being developed by Roche Holding AG showed promising results in a small, early stage trial involving children with medulloblastoma, the most common type of malignant brain tumor in children.
The drug, GDC-0449, is part of a new class of medicines that block the Hedgehog signaling pathway, which involves several proteins that play a role in cell growth
Medulloblastoma research currently funded by the National Brain Tumor Society
2010 Standard research grant
Anna M. Kenney,PhD
Memorial Sloan-Kettering Cancer Center
New York, New York
YAP1 as an effector of Sonic hedgehog mitogenic signaling in cerebellar development
This pediatric study will compare how the protein YAP1 causes cells to divide in healthy brain and in medulloblastoma, identify its role in medulloblastoma recurrence, and implement genetic engineering to develop new medulloblastoma mouse models based on YAP1 activity. Medulloblastomas arise from rapidly dividing immature brain cells, which divide when they receive an instructive signal from a molecule called “Sonic hedgehog”. Researchers recently found that in dividing brain cells Sonic hedgehog turns on YAP1 which can cause cells to become cancerous. Preliminary studies show that YAP1 proteins in medulloblastoma cells survive radiation and cause tumor re-growth, making it an essential target for future therapies.
2010 Advanced Research Grants
James Waschek, PhD
University of California
Los Angeles, California
Critical role of STAT3 in medulloblastoma immune evasion in genetically engineered mice
The objective of this project is to genetically distinguish the consequences of STAT3 activation in medulloblastoma tumor cells vs. the immune cells that invade the tumors. STAT3 activation is thought to be a critical event in the development of brain tumors and a suggested therapeutic target. However, STAT3 is also important for the ability of the immune system to help fight tumors. Genetically engineered mice afford a new possibility to determine mechanisms by which the natural immune response changes as tumors progress from very early to later stages.
Cognitive Rehabilitation: The Evidence, Funding and Case for Advocacy in Brain Injury November 2006
Impairments of cognitive function are among the most common and important problems that lead to disability after acquired brain injury. Treatment of cognitive dysfunction is central to the treatment and recovery of individuals with brain injury because of the widespread impact of cognitive rehabilitation deficits on safety, functional independence, productive living, and social interaction. Yet, individuals with brain injury often have difficulty obtaining treatment for cognitive dysfunction, termed “cognitive rehabilitation.”
What is a clinical trial?
A clinical trial is a research study of new therapies (or experimental drugs and treatments). By studying a larger collected group of children in a protocol with very exact treatment guidelines, doctors are able to draw better conclusions about how effective a treatment is and work to improve it.
The National Cancer Institute (NCI) oversees a large cooperative group of over 240 hospitals, the Children’s Oncology Group (COG), that develop new treatments for children with brain tumors, share information, and have common goals. The Pediatric Brain Tumor Consortium (PBTC) is a second NCI sponsored organization that has clinical trials specifically designed for children with brain tumors.
By enrolling in a clinical trial, the child may be the first to receive new therapies before they become more widely available; they often times become standard treatment. By evaluating new therapies for large numbers of children through COG or PBTC, researchers can more quickly and efficiently gather information about effective therapies.
Phases of Clinical Trials
Clinical trials are often describes as being phase I, phase II, or phase III.
Phase I trials are done to evaluate the side effects of a new treatment and to establish the proper dose. Different patients may receive different doses of the same medicine. Although doctors hope that the treatment may help the patient, that is not the main goal of a phase I clinical trial. After a phase I trial has been completed and the proper dose of the new medicine has been determined, a phase II trial may begin.
In a phase II trial, all of the patients receive the same dose of the medicine and the goal is to see how effective the new treatment will be. If a phase II trial finds that the new treatment is very promising, a phase III trial may be done.
In a phase III trial, patients are randomly given one of two different treatments. A phase III trial is usually done to find out whether a new treatment is better than, worse than, or the same as the established treatment for the disease.
Current Clinical Trials
- Combination Chemotherapy With or Without Etoposide Followed By an Autologous Stem Cell Transplant in Treating Young Patients With Previously Untreated Malignant Brain Tumors (phase III clinical trial)
- Proton Beam Radiotherapy for Medulloblastoma and Pineoblastoma (phase II clinical trial)
- Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor (phase I clinical trial)
- Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor (a pilot study)
- Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors
- ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors (phase I clinical trial)
- Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma (phase III clinical trial)
- Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor (phase III clinical trial)
- GDC-0449 in Treating Young Patients With Medulloblastoma That is Recurrent or Did Not Respond to Previous Treatment (phase I clinical trial)
What New Treatments Can We Expect in the Future
Many children’s tumor specialists expect to see advances in several areas: less traumatic surgeries, new chemotherapeutic drugs with fewer side effects, and combinations of drugs that effectively could replace surgery and radiation therapy, treatments that support the body’s own immune system to kill tumor cells, and gene therapy.
- Intrathecal therapy (medicine directed into the cerebrospinal fluid) is being explored in medulloblastoma in pre-school children as part of brain sparing strategies and as an alternative to unacceptably neurotoxic radiation.
- High dose chemotherapy with autologous peripheral stem cell rescue This is a technique in which certain cells in the body known as stem cells are used to replace other, depleted cells, such as immune cells and blood cells that are destroyed during high dose chemotherapy.
As more is learned about the molecular events in a cell that make it lose control, drugs that inhibit the loss of control are also being increasingly tested. Instead of attacking the tumor directly, some new drugs are targeted at the tumor’s blood supply in an attempt to starve the tumor.
The results of these treatments are promising, but it is too early to tell which therapy provides the best hope for killing all the tumor cells with the fewest long-term side effects. Research must continue in specialized medical centers and children’s hospitals.