Brain Tumor Breakthrough

April 29, 2014 — 2 Comments

It’s been over two and a half years since Ayden was diagnosed with Medulloblastoma and I started this research journey. Lots of dead ends trying to separate the wheat from the chaff. Then reading too many PubMed articles to imagine, I narrowed Ayden’s cancer to a CMV driven cancer. I finally am seeing others write-up this same conclusion. Finally the ball is gaining momentum and people are living longer due to this new course of treatment. Next up, move beyond Glioblastoma, and begin running clinical trials with Medulloblastoma, Neuroblastoma, Prostate, Lung and Breast cancer. Then we need to look at CMV and other opportunistic pathogens as drivers of late term effects of all cancer survivors.

Overview of CMV as a driver in Glioblastoma

Viral Cancer I’ve written often about the fact that 99% of Glioblastoma and 92% of Medulloblastoma show active CMV infections  and show signs that CMV has hit and run certain tumor cells making genetic and epigenetic changes.  

Now researchers are testing Neuroblastoma for CMV and the latest research shows 100% of the tumors showed signs of CMV or cyclomegalovirus.  This continues to reinforce that brain cancers key consistent factor is the triggering of oncogenisis  is by a viral infection that over expresses oncogenes and disables key anti-oncogenes thus driving these devastating cancers and leads towards potential opportunities for new and less devastating treatment options including using anti-virals like Valcyte. 

https://www.dropbox.com/s/kz18ub4qbkjj2gy/ijc28265.pdf

Viral Cancer

Genes are biological chemical software routines that do specific tasks in our bodies. Oncogenes are genes that have been proven to contribute to the development and growth of cancer.  There are approx. 50 distinct Oncogenes known and some that are found often over expressed in Medulloblastoma are MYC , MYCN and TAG. MYC and MYCN alone cause many hallmarks of cancer. When these genes are ran, they accelerate DNA replication, they turn off programmed cell death in two ways, drives new blood vessels to the cell / tumor and more (footnote ***).

Anti-Oncogenes are genes with the ability to police Oncogenes and keep them from going out of control and causing cancer (The most common damaged Medulloblastoma Anti-oncogene is P53 also known as TP53. There are two copies of TP53 and both must be damaged for this gene to be silenced (footnotes * **). When cancer happens, a couple basic things happen:

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USC confirms CMV as a Cancer causing Oncovirus and drive the most common salivary cancers.

http://www.news-medical.net/news/20111116/Study-confirms-link-between-CMV-and-mucoepidermoid-carcinoma.aspx

An important new study from the Laboratory for Developmental Genetics at USC has confirmed cytomegalovirus (CMV) as a cause of the most common salivary gland cancers. CMV joins a group of fewer than 10 identified oncoviruses – cancer-causing viruses – including HPV.

The findings, published online in the journal Experimental and Molecular Pathology over the weekend, are the latest in a series of studies by USC researchers that together demonstrate CMV’s role as an oncovirus, a virus that can either trigger cancer in healthy cells or exploit mutant cell weaknesses to enhance tumor formation.

Lead author Michael Melnick, professor of developmental genetics in the Ostrow School of Dentistry of USC and Co-Director of the Laboratory for Developmental Genetics, said the conclusion that CMV is an oncovirus came after rigorous study of both human salivary gland tumors and salivary glands of postnatal mice.

CMV’s classification as an oncovirus has important implications for human health. The virus, which has an extremely high prevalence in humans, can cause severe illness and death in patients with compromised immune systems and can cause birth defects if a woman is exposed to CMV for the first time while pregnant. It may also be connected to other cancers besides salivary gland cancer, Melnick added.

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HCMV is found is 99%+ of Glioblastoma Brain Tumors.  Researchers are now beginning to measure the level of CMV infection in the tumors as a prognostic marker for expected survival.  The research shows that Low Levels of CMV in a Glioblastoma tumor correlates to survival beyond 18 months.  Actively treating CMV in Glioblastoma has a direct and positive improvement in patients survival length.  This issue needs further research and the same research applied to other cancers to improve their survival rates.

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Dr Cobb was early, if not the first to connect CMV to Brain Cancer. Here he writes in a Blog on the current state on the usage of anti-viral story extend brain cancer lives:

Dr. Cobb on CMV treatment with Antivirals

A listing of genes that have found to be altered by each specific Cancer.  This shows on the genetics side the diversity of genetic defects driving cancer.  

Cancer is a very complicated disease.  In fact calling it one disease is likely a mistake.  Even naming a cancer like brain cancer turns into more specialized names like Medulloblastoma, Glioblastoma, Neuroblastoma, DIPG, Pineoblastoma, etc.  Then for Medulloblastoma for example there is WNT, SHH, Group 3 and Group 4 (with new talk about sub-types inside of these sub-classifications) and grades of the disease beyond that.  

With the emergence of genetic profiling of tumors, we are just beginning to unravel the actual genetic defects that contribute to cancer tumor creation and growth.  This alone clearly shows that all cancers are not created equal.  I am including a link to here that shows the list of genes known associated with cancer and what cancers they are associated with:

https://www.dropbox.com/s/8v886t6pg3rusdq/cancer_gene_census.xls

You will clearly see, each cancer from a genetic point of view is very unique.   There is emerging research going on that genetics, the actual defect of a gene either from birth or a defect later may only account for about 10% of the reasons driving cancer.  There is another field called Epigenetic’s that seems to be really driving cancer growth.  If you think of a gene in your body as a software program like on a computer that does a specific thing, it will help thinking about this analogy. 

There are Oncogenes that are genes in every cell in our body that help recreate the “hallmarks of cancer”, like creating new blood vessels to feed a tumor “Angiogenesis” or stopping cell programmed death so they live too long (Apoptosis) and speeding up DNA / cell replication.  These Oncogenes can be copied multiple times in the chromosomes (copied and pasted again).  Or Viruses can bring a new copy of an Oncogene and put it in a cell (an example Oncogene would be MYC, but we have a few dozen in every cell of our bodies).  Then, there are anti-Oncogenes.  These genes (or chemical software programs) actually watch for these behaviors of Oncogenes and try to keep them under control.  Sometimes in cancer, these Oncogenes are damaged.  Sometimes one chromosome / gene entry will be copied on top of an Anti-oncogene, thus damaging and disabling that oncogene.  These are all genetic defects that can lead to cancer.   Epigenetic’s determines when a gene should run and how often.  Consider it like the scheduler that determines whose turn it is to run and how often it should run.  In cancer, unfortunately, this scheduler on a gene by gene basis gets reprogrammed.  For Oncogenes, the scheduler gets turned on, when it should be off, or turned up so it’s running much more often causing things like fast DNA replication.  Anti-oncogenes get reprogrammed so they don’t run or don’t run as often.  

So each cancer has it’s unique combinations of one or more Oncogenes being over expressed either by genetic or epigenetic reasons.  Each cancer has it’s unique combination of one ore more Anti-Oncogenes being under expressed either by genetic or epigenetic reasons.