Canadian Research Breakthrough Holds Promise for Development of Effective Cancer Therapies
Scientists identify new target for cancer cure
Montreal and Toronto, September
2, 2009 – Researchers Dr. Marc Therrien at the Institute for
Research in Immunology and Cancer (IRIC) of the Université de Montréal,
and Dr. Frank Sicheri, at the Samuel Lunenfeld Research Institute of
Mount Sinai Hospital in Toronto, have discovered a new target that may
be instrumental in the development of new, more effective cancer
therapies.
A recent article co-authored by
Drs. Therrien and Sicheri and published in the leading scientific
journal Nature sheds new light on the activation mechanism of
the RAF protein kinase which, when mutated, is responsible for more
than 25 per cent of cancers. Understanding this mechanism may lead to
novel anti-cancer agents designed to minimize the toxic side effects
caused by chemotherapy.
The RAF family of kinases
regulates various cellular processes including cell growth,
differentiation and survival. The Therrien-Sicheri team is the first to
show that the dimerization, or combination, of two RAF proteins is
essential to its activation. Inhibiting the dimerization of RAF may
therefore block its activation, thus stopping cancer cells from
growing. The study exposes not only the activation mechanism of RAF,
but potentially the mechanisms that control other protein kinases, a
large number of which are linked to cancer and other diseases such as
diabetes, hypertension and neurodegeneration.
“Basic researchers believe that
one of the most promising strategies to finding lifelong cures for
cancers lies in understanding the molecular underpinnings specific to
cancer cells,” explains Dr. Therrien, “It is hoped that this will
translate to the development of inhibitors tailored to specific
molecular defects and, as a result, should increase the effectiveness
of new target-based cancer therapies.”
“Protein kinases are the targets
for some of the most successful anti-cancer drugs in the clinic,” says
Dr. Sicheri. “Now that we have discovered how to turn off the RAF
protein without interfering with other proteins, we may be able to
design drugs that have unprecedented precision in targeting cancer
cells while reducing the toxic side effects for patients.”
The Therrien-Sicheri team intends
to jointly pursue work in this area to identify drug-like molecules to
block the dimerization process of RAF, which may possibly lead to the
discovery of new classes of anti-cancer agents.
Researchers & Financing
Dr. Marc Therrien holds the
Canada Research Chair in Intracellular Signalling. Dr. Frank
Sicheri was the recipient of a Canadian Cancer Society Research
Scientist Award. The research received funding from the Canadian Cancer
Society and the Canadian Institutes for Health Research.
About the Institute for Research in
Immunology and Cancer
IRIC is a state-of-the-art biomedical research centre at the
Université de Montréal. IRIC is committed to finding novel cancer
therapeutics through multidisciplinary approaches. Its team of more
than 350 scientists and professionals work on various aspects of cancer
research from basic science through to clinical applications. For more
information about IRIC, please visit www.iric.ca. For more information about
Dr. Marc Therrien, please visit http://www.iric.ca/Recherche/Chercheurs/Therrien_M_EN.html.
About the Samuel Lunenfeld Research
Institute of Mount Sinai Hospital
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a
University of Toronto affiliated research centre established in 1985,
is one of the world's premier centres in biomedical research.
Thirty-four principal investigators lead research in diabetes, cancer
biology, epidemiology, stem cell research, women's and infants' health,
neurobiology and systems biology. For more information on the Samuel
Lunenfeld Research Institute, please visit www.lunenfeld.ca.
Paper cited:
Thanashan Rajakulendran, Malha Sahmi, Martin Lefrançois, Frank
Sicheri and Marc Therrien. “A Dimerization-Dependent Mechanism
Drives Raf Catalytic Activation.” Nature, prepublished online 02 Sept,
2009; DOI: 10.1038/nature08314
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