Viral Oncology

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Introduction

Electron micrograph of the Ebola Zaire virus. This was one of the first micrographs taken of the virus, in 1976. By Dr. Frederick Murphy, now at U.C. Davis, then at the CDC.

By Erick Ditmars

Viral oncology is a subsection of Oncology that focuses on treating tumors with viruses and is the most recent and arguably most promising new age tool we have for treating cancer. While this field has gotten a lot of press in recent years the idea of using viruses as oncolytic agents has been around since the early 1920’s, since as early as the mid-1800’s doctors noticed that certain illnesses would cause remission in cancer patients. These patients usually had blood based cancers such as leukemia or lymphoma with significant immune suppression. The most famous report of this type was made by Dock1 in which a 47 year old woman with “Myelogenous leukemia” went into remission after a flu infection. This report was first made in 1896, a whole 37 years before influenza was proven to be caused by a virus. Another more shocking case is that of a 4 year old boy with lymphatic leukemia who contracted chickenpox. His liver and spleen and lymph nodes were all severely swollen and his leukocyte count was greatly elevated (200 cells/ul) after contracting chicken pox his liver, spleen returned to normal size and his white count fell back into normal levels (4.1 cells/ul). However, in both cases the remission was short lived and the cancer soon returned. The first attempt to use viruses in oncology was the treatment of Hodgkin’s lymphoma with hepatitis in the 1950’s. While some did achieve remission for a short time many in the study also contracted Hepatitis B. The study was discontinued. A number of similar experiments were run throughout the 50’s and 60’s with minimal success and viral oncology was largely abandoned. It was almost 50 years later when a breakthrough in viral oncology came in the form of oncolytic adenovirus H101. This virus was approved by the FDA for cancer treatments in 2005 and works by targeting p53 deficient cells (most cancers are p53 deficient). Today there are many different viral pathways that medical research is focusing on in an attempt to make viruses an essential part of the cancer fighting toolbox.
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Legend/credit: Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.
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Introduce the topic of your paper. State your health service question, and explain the biomedical issues.

Why Viruses?

For a long time after the correlation between viral infection and cancer remission was first discovered researchers wondered why cancer cells made such good hosts for viral cells. It wasn’t until we began to understand the molecular and genetic mechanism behind cancer that that relationship started to become clear. Cancer cells are the product of small scale evolution which is to say that the accumulation of point mutations and chromosomal shifts result in something called chromosomal instability have resulted in a phenotype drastically different from its ancestor. Typically in cancer cells we see a selection for growth advantages over somatic cells. These increased growth factors include immunity to density and anchorage dependence as well as repression of certain apoptosis measures and the activation of genes that would not normally be transcribed, such as telomerase. While these genetic and molecular changes result in a massive increase in fitness when compared to somatic cells, often times certain defensive mechanisms are sacrificed. For example in many cancer cells a number of genetic repair enzymes are shut off as well as proteins that defend against mutations in the genome and foreign DNA. It is these defense deficits seen in so many cancer cells that viruses exploit. Without the ability to defend against foreign DNA many cancer cells are left vulnerable to most viruses. By exploiting the innate viral sensitivity of most cancer cells scientists have been able to engineer viruses that can selectively kill cancer cells and grant immunity towards cancer cells.

Section 2

Include some current research, with at least one figure showing data.

Section 3

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References

[1] Hodgkin, J. and Partridge, F.A. "Caenorhabditis elegans meets microsporidia: the nematode killers from Paris." 2008. PLoS Biology 6:2634-2637.

Authored for BIOL 291.00 Health Service and Biomedical Analysis, taught by Joan Slonczewski, 2016, Kenyon College.