Inside Salk - October 2009 - page 8

This year, Shaw published a study that demonstrat-
ed how he used rapamycin, an immunosuppressant
drug normally prescribed to prevent organ transplant
rejection, to drastically reduce tumors in labmouse
models developed tomirror Peutz-Jeghers syndrome,
a rare cancer of the colon in which patients inherit
a mutated copy of the LKB1 gene.
He got the idea after first linking LKB1, a tumor
suppressor also commonlymutated in lung cancer,
to AMPK, a protein involvedwith glucose produc-
tion. Further studies by his team revealed that AMPK
regulates TOR, an oncogene that is highly expressed
in cancer (its name is short for Target of Rapamycin).
Shaw then asked the question: Will rapamycin
work on LKB1-deficient tumors to block TOR activity?
He found out that it does. Themassive tumors that
had developed in themice’s colons drastically shrunk
in size andwere stabilized in the experiments.
“This is a wonderful example of being able to use
basic research and geneticmodeling to treat human
disease,” Shaw says. “We basically put themice
through a clinical trial and test themwith different
doses of rapamycin.”
Current studies in Shaw’s lab are examining wheth-
er these same therapeutic approaches will work in a
mousemodel they have developed for lung cancer.
Work by
RonaldM. Evans
, professor
in the Gene Expression Laboratory, led
to the discovery of a family of nuclear
hormone receptors, amember of which –
the estrogen receptor (ER) – is now known
to contribute to the development of breast
cancers when expressed at high levels.
Another nuclear hormone receptor, the
retinoic acid receptor (RAR), plays a key
role in promyelocytic leukemia when joined to the
product of a second gene.
“The fundamental progress in cancer research
over the last 30 years has been to identify specific
genes that cause cancer,” Dulbecco says. “Once the
genes responsible for cancer have been identified,
you canmove forward to therapy.”
Founded in 1970 by
Jonas Salk
and designated
anNCI Center in 1973, the Salk Institute Cancer
Center is led by
Tony Hunter
, an American Cancer
Society professor in theMolecular and Cell Biology
Laboratory. His discovery of tyrosine phosphoryla-
tion, a key event in normal cell growth which can
drive tumor cell proliferation when unregulated,
eventually led other scientists to develop a new
generation of cancer drugs, including Gleevec
– a leukemia drug whose developers received the
Lasker Prize for their work inOctober.
The Cancer Center ismade up of three distinct
research programs: Metabolism and Cancer, Mouse
Models and Stem Cells, and Growth Control and
Genomic Stability. Thirty of Salk’s 57 principal
investigators, 161 postdoctoral researchers, and
70 graduate students are part of the Center, which
continues tomake new breakthroughs with poten-
tial for new therapeutic strategies.
LikeWahl’s, some discoveries are born from
unorthodox ideas.
To hear
Reuben Shaw
discuss his latest
experiments using compounds to treat
cancer, visit
In the long runwhat we hope is that if enough cancer
genomes are sequenced, commonalities will begin to
emerge for a particular cancer type so that they can be
correlatedwithmore effective treatment.
Inside SalkOctober 2009
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