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Dr. Charles Roberts, Dana Farber Cancer Institute
My team has studied the SNF/SWI gene complex for several years and just published a key mechanism by which
SNF5 gene loss causes formation of certain cancers. Mutations in SNF5 are present in the large majority
of malignant rhabdoid tumors (MRT), a highly lethal cancer that occurs in the kidneys, brain, and soft tissues of young children,
as well as in a variety of adult cancers. Contrary to accepted models, my team demonstrated that SNF5 loss does not inactivate
(or permanently mutate) the entire gene complex but rather leads to its epigenetic malfunction. It is this
malfunction that drives cancer formation and growth. This distinction is critical because my team has shown
that targeted inhibition of this aberrant activity causes regression of the cancers – the first time this regression
has ever been achieved.
Continued funding from the Garrett B. Smith Foundation will enable my lab now to begin pursuit
of two avenues of research into promising therapies. These studies have a high degree of therapeutic relevance
because, unlike genetic mutations, epigenetic changes are potentially reversible; and, several early drugs aimed at altering
the epigenetic state of cancer cells have already been FDA approved. We will utilize our uniquely engineered
Snf5 mouse models to specifically identify drugs which have the potential to counteract the growth-promoting effects of the
malfunctioning SWI/SNF complex. Additionally, by pursuing a targeted screen utilizing an shRNA library
that we have obtained via collaboration with the laboratory of Dr. Steven Elledge, we will identify the essential cancer growth-promoting
genes that are activated in the absence of SNF5. These genes will also constitute ideal targets for new drugs.
In recognition
of both these achievements and of their further promise, the American Association for Cancer Research named Dr. Roberts as
one of the 13 most innovative and promising young cancer researchers nationwide via its “Stand Up to Cancer” initiative
on December 7th, 2009. Most certainly, the support provided by the Garrett B. Smith Foundation allowed us to attain this honor
and to reach this exciting, new phase of research. Thank you again for your longstanding generosity and for considering renewed
support.
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