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Treatment Advances in Medulloblastoma
Shane [email protected] Sciences
Thesis Director: Dr. Mark Jaroszeski
Prospectus
The issue of medulloblastoma is currently being personified as the poster child of
pediatric neuro-oncology. It is the most common malignant pediatric brain tumor (Huang
2015). Medulloblastoma is characterized by a metabolically active mass of tissue in the brain
that starves the brain of nutrients and compresses the surrounding cells, potentially sending
stimuli to the surrounding cells and simulating death signals. This particular genre of cancer
spreads through the cerebrospinal fluid, categorizing it as an immensely deadly disease.
Apoptosis, the process by which cells are pre-programmed to kill themselves usually as a
defense mechanism, has been thoroughly studied and is already understood. Cancer cells
sometimes elicit apoptotic responses, resulting in deterioration of bodily tissue. At steady-state
cell life, a group of cells can divide and die at the same rate and so you will neither accumulate
nor run out of cells. A tissue can acquire a set number of mutations at which point that cell can
now hide from the immune system and change growth kinetics. Once you change the balance
or cell growth or death, you grow a tumor. Cancer starves the body and tissues and once it
metastasizes, it grows even larger.
The immune system attempts to distinguish between what are normal body cells from a
wide variety of external agents. T-cells found in the human body’s immune system are
continuously attempting to remove cancerous cells through apoptotic cascades. PD1 is a
programmable death receptor on the surface of T-cells, and is currently one of the most studied
topics in Oncology. Many cancer cells secrete a PD1 ligand that binds to PD1 receptors on T-
cells causing them to be driven into apoptosis. Cancer-derived antibodies are able to neutralize
the PD1 ligand, which is no longer able to bind to the PD1 receptor and the T-cells are still able
to function. Ketruda (pembrolizumab) is an anti-PD1 antibody that has been released by Merck
& Co. for stage 3 metastatic melanoma, the 3rd deadliest cancer in the US. The Hedgehog
Pathway is a major regulator of fundamental processes in the body such as coordinating cell
growth and development, and is currently being studied as a means of medulloblastoma
treatment (Huang, 2015). We can also see that the research being done into vascular
endothelial growth factors, which are directly involved in immunosuppression and angiogenesis
in tumor biology, prove as potential for new therapy (Johnson, 2007).
Cancer patients are ostensibly noticed getting smaller as prognosis continues. Many are
under the impression that this is due to the effect of cancer “eating away” at the body,
however in actuality it is due to starvation of healthy regions of the body by the cancerous cells.
This is a booming area of research where biologics and genes are now being used to attack
those genes and cancers. If you could take a biopsy of a tumor and conduct a gene assay on the
sample, we can find mutations and design a gene, drug or antibody. Chemotherapy has been a
popular reaction to the discovery of cancer in a body, but it is actually a means of supplying
enough poison that doesn’t kill the entire body. The process by which chemotherapy operates
does not directly target anything, and many times it can result in the development of cancerous
cells through ingestion of carcinogenic compounds in the treatment. We can see that the
modulation of our immune system can be the perfect vehicle for destroying tumor cells
(Bustamante Alvarez, 2015). The problem is that we need to develop a technique to train the
immune system to carry out the appropriate response. Though gene therapy at the cell-
response level can potentially be used to treat cancer, most pre-existing research on the
subject has been derived from animal research and clinical trials.
Cancer is notoriously known for inducing a change in a person’s diet. As such, it may not
be farfetched to suggest dietary modifications and alternative medicine as a means of curing
the aforementioned disease. Ketogenic, paleo, low-sugar and organic diets have been
anecdotally known to positively contribute to the treatment of certain types of cancer (Hao et
al, 2015). This stems from the fact that cancer cells metabolize these materials and induce the
activity of the cancer. As mentioned previously, tumorigenic cells starve the body of nutrients in
order to thrive, so to determine a way in which you can starve the body of the nutrients which
the cancer cells need while keeping the rest of the body of the patient fully functional can be a
potential solution (Kapelner & Vorsanger, 2015).
Combination therapies (multi-faceted treatments comprising the use of chemotherapy,
antibodies, radiation, modulation of the immune system and gene therapy) are proposed to be
the most effective means of treatment of the disease. Etoposide plus radiation therapy
followed by combination chemotherapy has been one recently tested treatment in children
with newly diagnosed advanced medulloblastoma (Children’s Oncology Group, 2014). Despite
aggressive treatment involving surgery, chemotherapy, radiation and other therapies, most
patients suffer devastating side effects. Thus, the development of new treatment strategies is
urgently needed. The focus of this study will be to compile past and current information and
potentially determine the best means by which medulloblastoma could be treated given recent
advances that have been made within the field of oncology.
Proposed Work Schedule
October 30th – Submission of Prospectus
November 1st – January 10th – Data collection, biweekly meetings with Dr. Jaroszeski
January 11th – Submission of 1st draft to the Chair
February 12th – Submission of 2nd draft to the Chair
March 25th – Submission of completed manuscript to the Chair, schedule defense presentation
April 8th – Preparation for final defense
April 15th – Final revisions and preparation of manuscript for formatting review
Works Cited
Bustamante Alvarez, J. G., et al. "Advances in Immunotherapy for Treatment of Lung
Cancer." Cancer Biol Med 12.3 (2015): 209-22. Print.
Children’s Oncology Group; National Cancer Institute. Etoposide Plus Radiation Therapy
Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed
Advanced Medulloblastoma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National
Library of Medicine (US). 2000- [cited October 20th 2015]. Available from:
https://www.clinicaltrials.gov/ct2/show/NCT00003573 NLM Identifier: NCT00003573.
Hao, G. W., et al. "Growth of Human Colon Cancer Cells in Nude Mice Is Delayed by Ketogenic
Diet with or without Omega-3 Fatty Acids and Medium-Chain Triglycerides." Asian Pac J
Cancer Prev 16.5 (2015): 2061-8. Print.
Huang, S. Y., and J. Y. Yang. "Targeting the Hedgehog Pathway in Pediatric
Medulloblastoma." Cancers (Basel) 7.4 (2015): 2110-23. Print.
Johnson, B. F., et al. "Vascular Endothelial Growth Factor and Immunosuppression in Cancer:
Current Knowledge and Potential for New Therapy." Expert Opin Biol Ther7.4 (2007):
449-60. Print.
Kapelner, A., and M. Vorsanger. "Starvation of Cancer Via Induced Ketogenesis and Severe
Hypoglycemia." Med Hypotheses 84.3 (2015): 162-8. Print.
Word Count
Prospectus word count: 875 words
