2009-12-08
The William Dameshek Prize, named
for the late past ASH president and the original editor of Blood, is awarded
each year to an individual who has made an outstanding contribution to
hematology over the preceding years. Dr. Louis M. Staudt of the National Cancer
Institute’s Center for Cancer Research in Bethesda, MD, is the recipient of the
2009 Dameshek Prize for his landmark contributions to the diagnosis and
treatment of lymphomas. The award ceremony will take place this morning at 9:30
in Hall F of the Ernest
N. Morial
Convention Center.
Dr. Staudt pioneered the use of
gene expression profiling to delineate clinically distinct lymphoma subtypes
and molecular predictors of survival. His work also showed that each molecular
subtype of cancer has its own vulnerability — critical weaknesses that can be
explored by loss-of-function RNA interference-based genetic screens.
Collectively, Dr. Staudt’s work has led to important new insights into pathways
of lymphomagenesis, as well as into the interactions of the malignant cell with
its environment. Dr. Staudt said, “The most gratifying aspect of this award is
the recognition that our ideas regarding the molecular diagnosis of cancer are
beginning to have an impact on the care of patients.”
Dr. Staudt feels that the greatest
accomplishment of his career has been the delineation of diffuse large B-cell
lymphoma (DLBCL) subtypes and their molecular pathogenesis. “After defining
subtypes of DLBCL by gene expression profiling, my laboratory showed that the
subtype that is most refractory to our current therapies, termed activated
B-cell-like (ABC) DLBCL, depends on signaling through the NF-κB pathway and
accumulates somatic mutations that spontaneously engage this pathway.” Together
with Drs. Wyndham Wilson and Kieron Dunleavy, Dr. Staudt conducted clinical
trials at the NCI that blocked the NF-κB pathway with the proteasome inhibitor
bortezomib, in conjunction with multi-agent chemotherapy. “We were very encouraged
when the results showed a much higher than expected survival rate in patients
with ABC DLBCL with this approach,” said Dr. Staudt. In the future, he expects
that his genomic investigations will lead to more targeted therapies aimed at
the “Achilles’ heel” of lymphomas, which will ultimately improve the survival
of patients.
Dr. Staudt said, “I think the
biggest and most rewarding challenge of my work has been to develop a
successful collaboration among eight international institutions, known as the
Lymphoma/Leukemia Molecular Profiling Project, to effectively address
clinically important questions in the lymphoid malignancies using genomics
technologies.” Dr. Staudt has enjoyed the fact that quantitative approaches
using genomic technologies have been able to make sense out of complex clinical
problems, and he imagines a future in which most cancer diagnoses will be
based, at least in part, on a molecular definition of the disease process.
“In a sense, my interest in the
genomics of human lymphomas began with a fairly obsessive interest in computers
as a high school student.” As an undergraduate and as an MD-PhD student, Dr.
Staudt became fascinated with the molecular machinery of B lymphocytes, an
interest that led him to investigate basic mechanisms of B-cell differentiation
with David Baltimore at the Whitehead Institute. He then took a job in the
Metabolism Branch of the NCI where the Chief, Tom Waldmann, was conducting
patient-oriented research in human T-cell lymphomas.“I was inspired to use my
interest in B-cell biology to understand the human malignancies derived from
these cells. I was able to dust off my computer science skills to apply the
fruits of the human genome project to the study of human lymphomas.”
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