Inside Salk - October 2009 - page 10

Inside SalkOctober 2009
“These are proteins that are working like anti-tumor suppressors,”Wahl explains.
“When they bind to p53, the cell can no longer sense DNA damage or initiate the
cell death program.”
His lab is nowworking on developing new compounds that impedeMdm2 and
Mdmx’s ability to bind to p53 and restore the gene’s normal protective function.
“It’s rare for academia to go into drug discovery experiments, but we felt it was
important for us to do so, andwe also feel these compounds will be very valuable
research tools,”Wahl says.
Themost recent studies at the Salk involve research of stem cell-like cells and
their relationship to cancer. It’s a very new field that may providemore answers
and possibly new treatments in the future.
Teams of scientists in the Verma and
FredH. Gage
labs, for example, are using a
model for glioblastoma, the deadliest andmost common brain cancer in humans, to
uncover the nature of specific cancer cells that are capable of spawning new tumors.
“There is increasing evidence that there is a population of cells inmost cancers
that have stem cell-like properties,” Hunter says. “It’s a field that’s in flux at
the moment because how these cells acquire these properties is unclear. There is a
school of thought that you have to target these tumor-initiating cells because if you
only kill off the rest of the tumor, then it doesn’t matter because they simply regrow.
“Chromatin reprogramming is a critical step in the genesis of stem cells and this
appears to be true of the stem cell-like cells in tumors,”Hunter says.
A recent finding from the Wahl and
Juan Carlos Izpisúa Belmonte
groups has
shed light on this idea. They found that p53 itself acts as a block to chromatin
reprogramming in somatic cells, suggesting that the lack of p53 inmost tumorsmay
predispose cells in these tumors to undergo reprogramming and adopt stem-cell like
fates. (See story on page 20.)
As a result, there is now a heightened interest in using new-generation inhibitors
that will block chromatin reprogramming as new types of cancer therapy. The Evans
lab is currently testing one novel inhibitor developed by his team on colitis-associat-
ed colon cancer in labmousemodels.
“The Salk Cancer Center has a history of significant contributions that have led to
a deeper understanding and treatments for cancer,”Hunter says. “Over the next few
years, new findings hold the promise to lead to new types of cancer drugs, and to
alleviate the mortality and suffering from this terrible disease.”
The fundamental progress in cancer research over
the last 30 years has been to identify specific genes
that cause cancer. Once the genes responsible for
cancer have been identified, you canmove forward
to therapy.
JuanCarlos IzpisúaBelmonte
FredH. Gage
Inder Verma
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