Cancer Study Cracked Code


Cancer was once considered to be the result of various malfunctions in cellular reproduction and the human immune system, which is charged with regulating cellular deformities that result from botched attempts by cells to reproduce themselves.  The resultant mutant cells, if not eliminated, were said to spread throughout the body in the same manner as a virus, until the process killed the patient. Further research indicated that such malfunctions could be caused by external factors, such as exposure to radiation, carcinogens, certain minerals (i.e. asbestos) and a plethora of other substances once thought completely unrelated to the disease. At this point it appears that modern medicine studies may have cracked the code for the cause of cancer.

Along with material or incidental causes of malignancy there also exists another, albeit much rarer, cancer-causing agent: viruses. Since the 1920s humans have known that viruses (often called “oncoviruses”) could cause cancer in animals. It was not until the 1960s that a human oncovirus was identified, and it was even later that the cancer-causing virus was decoded providing the knowledge used by later oncovirus researchers.

Since that time further study of the already-identified virus lead scientists to discover many more oncoviruses, including the Kaposi’s sarcoma-associated herpes virus and the human T-lymphotropic virus. In 2008, a pair of virologists, Yuan Chang and her husband Patrick Moore, began to unravel the mystery of the deadly skin cancer Merkel cell carcinoma (MCC), a rare form of skin cancer which has been infecting increasing numbers of people since 1986. Despite advances in preventative medicine, new cases of the disease continue to increase,  so that even now it infects over 1,500 people every year. Chang and Moore had already discovered one oncovirus and used their expertise to analyze the possible existence of pathogenic origin of the strange cancer.

After closely examining cancerous tumors and blood of infected patients and subjecting the resulting data to rigorous statistical analyses, the researchers found evidence that proved their hunch correct: cells inside the blood and tumor samples that did not match MCC cells. Later analysis indicated that it was indeed a virus now called Merkel cell polyomavirus (MCP). This discovery, along with the outcome of their statistical analyses, gave them enough evidence to conclude that the virus did indeed cause Merkel Cell Carcinoma.

Although they had identified the virus and linked it to MCC, Change and Moore did not look very closely at the virus itself, nor did they attempt to discern the ways in which the virus actively caused cancer to occur and grow within the body. Their study, while revolutionary, was not the end of inquiry.

Five researchers from Philadelphia recently went back to look more closely at the virus. Their goal was very conservative and straightforward. Citing the extensive amount of information about the reproduction of other Polyomavirus pathogens (such as Simian virus 40 otherwise known as SV40) and the relatively small amount of literature relating to the replication of (MCP), they set out to “provide an initial framework for understanding” how the virus, which like SV40 lies dormant inside of infected cells for years, replicates itself while avoiding detection by its host.

Understanding the life-cycle of the cancer-causing virus is essential to any scientist who wishes to develop effective treatments for both the virus itself and the cancer it has been shown to eventually produce. Although it develops in only a very small number of people, MCC has a fairly low survival rate even among patients who begin receiving treatment during the earliest stages of the disease.

To achieve their stated goal the Philadelphia research team performed what they claimed to be the first  ever  “proteomic analysis” of the virus, which in this case simply means using a mass spectrometer to examine their virus-containing samples’ general content and then take a much closer look by utilizing other more specific tests. Their cancer study does indeed crack the virus’s code, in the sense that they indicate what it is made out of and what it contains, but the rest is left to their reasoning and familiarity with the functioning of pathogens. Their initial findings revealed that the Merkel cell polyomavirus likely reproduces in the same way as its relatives but that it remains latent by using a completely method.

The results of the research team indicate that MCP enters into the body of its host much in same way as its cousin Simian Virus 40 (SV40), but also that once inside it operates on an entirely different level of complexity. By studying the outcomes of the many tests which they applied to MCP the team was able to identify the virus’s three “phosphorylation sites” (protein chains which “activate” upon contact with phosphates) which mirrored those found in SV40.

The number of phosphorylation sites, however, is revealed to be the last similarity between the two polymaviruses.  Of those three sites, identified as T271, T297 and T299, the research team’s results strongly suggested that site T299 encouraged viral reproduction (similar to a site found in SV40) while binding site T297 “may negatively regulate viral replication.”Far from being some kind of evolutionary mistake however, the team reasoned that the two contradictory sites were used by the pathogen to control its own replication within its host cell and thereby maintain their status as a latent infection.

The other notable result of their investigation was site T271, which, as it turns out, is homologous to nothing found in SV40. This site is so mysterious that the team would not even venture a guess as to its function within the pathogen. They noted only that the mass spectrometer’s results indicated that it was “highly enriched” and was located in a unique region of the virus.

Experts hope that future scientists, researchers and doctors will be able to use the information contained within this study to build on top of  it and increase the currently minuscule body of knowledge concerning this virus and the cancer it produces. If that does indeed happen society may one day know the purpose of site T299 and how exactly the pathogen produces cancerous growths in its hosts. If eventually this cancer-causing virus code is definitively cracked, the growth of data, research and other clinical information will enable medical practitioners to develop better diagnostic tools and also more successful treatments than those currently exist.

By Andrew Waddell


Science Creative Quarterly
National Center for Biotechnology Information (NCBI)
Seminars in Cutaneous Medicine and Surgery

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