Cancer Gene Theory Challenged

December 1, 1996
Oncology, ONCOLOGY Vol 10 No 12, Volume 10, Issue 12

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.

Researchers at Roswell Park Cancer Institute have cast doubt onthe widely held belief that the mutation of the p53 gene triggersthe chain reaction of cancer development.

"At least not for colorectal cancer," asserted GarthAnderson, phd, a senior scientist who studied gene mutations inthis disease with colleagues at the Institute. "Clearly,p53 mutation plays an important role in cancer development, butit does not appear to initiate the multi-step process."

The results of this study appeared in the November 20th issueof the Journal of the National Cancer Institute.

This research breaks faith with dogma long held by the scientificcommunity regarding the role of the p53 gene in cancerous tumors.

"We can compare our investigation to another; the explosionaboard TWA flight 800 which most experts initially believed wascaused by a bomb," remarked Dr. Anderson. "The evidencejust wasn't there to support that conclusion, prompting a returntrip to the drawing board, or in our case, the laboratory."

p53 Function Not Lost in Rapidly Evolving Tumors

It has long been thought that mutations in the p53 gene causedthe 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 rapidlyevolving tumors had not lost p53 function. The p53 gene servesa regulatory function by binding DNA, which, in turn, controlshow cells grow and divide.

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

"This research is pretty clear. p53 is the last step, notthe first," explained Anderson. "There is somethingelse occurring: a mysterious enigma which controls cells and causesthem to progress to a cancerous state. If we can find this enigmaand shut down this process of instability, we can shut down thecancer process."

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

"The key question becomes, if not p53, then what?" asksMorton S. Kahlenberg, md of the Division of Surgical Oncologyat Roswell Park and a key member of the research team. "Weare now focusing on identifying what actually is or are the drivingfactors behind the predominant form of genomic instability seenin cancer; once found, these should become invaluable new therapeutictargets and important new diagnostic tools."