Cancer Gene Theory Challenged

November 06, 1996

BUFFALO, NY - Researchers at Roswell Park Cancer Institute have cast doubt on the widely held belief that the mutation of the p53 gene triggers the chain reaction of cancer development.

"At least not for colorectal cancer," said Garth Anderson, PhD, a senior scientist who studied gene mutations in this disease with colleagues at the Institute. "Clearly, p53 mutation plays an important role in cancer development, but it does not appear to initiate the multi-step process."

The results of this study are highlighted in the November 6 issue of the Journal of the National Cancer Institute.

This research breaks faith with dogma long held by the scientific community regarding the role of the p53 gene and cancer tumors.

"We can compare our investigation to another - the explosion aboard TWA flight 800 which most experts initially believed was caused by a bomb," remarked Dr. Anderson. "The evidence just wasn't there to support that conclusion, prompting a return trip to the drawing board, or in our case, the laboratory."

It has long been thought that mutations in the p53 gene caused the gene system to crash, creating a state called genomic instability. Looking at actual colorectal tumors and their genomic instability, the Roswell Park researchers discovered that patients with rapidly evolving tumors had not lost the p53 gene function. p53 serves a regulatory function by binding DNA, in turn controlling how cells grow and divide.

A series of mutations must occur before a normal cell becomes cancerous. Conventional wisdom said p53 played the central role when gene systems ran amok. That is simply not the case, Anderson says.

"This research is pretty clear. p53 is the last step, not the first," explained the scientist. "There is something else occurring - a mysterious enigma which controls cells and causes them to progress to a cancerous state. If we can find this enigma and shut down this process of instability, we can shut down the cancer process."

Such research also may lead scientists to determine how to make cancer cells less resistant to potentially effective chemotherapies.

"The key question becomes, if not p53, then what?" asks Morton S. Kahlenberg, MD of the Division of Surgical Oncology at Roswell Park and a key member of the research team. "We are now focusing on identifying what actually is or are the driving factors behind the predominant form of genomic instability seen in cancer; once found, these should become invaluable new therapeutic targets and important new diagnostic tools."

Roswell Park, founded in 1898, is the world's first cancer research and treatment center.

Roswell Park Cancer Institute

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