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," asserted 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 appeared in the November 20th 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 in cancerous 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."
p53 Function Not Lost in Rapidly Evolving Tumors
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 p53 function. The p53 gene serves
a regulatory function by binding DNA, which, in turn, controls
how cells grow and divide.
A series of mutations must occur before a normal cell becomes
cancerous. Conventional wisdom said that p53 played the central
role when gene systems ran amok. That is simply not the case,
"This research is pretty clear. p53 is the last step, not
the first," explained Anderson. "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
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."