Samuel Waxman Cancer Research Foundation funded cancer investigators discuss Aging and Cancer, among other key research topics, at the
SWCRF Breakthroughs 2015 Scientific Review and Symposium
Scientific gathering fetes celebrated cancer researchers
Siddhartha Mukherjee, MD, PhD and Robert A. Weinberg, PhD
|Funded researchers from the SWCRF Institute Without Walls at the May 3 - 4 Scientific Review and Symposium|
The growing incidence of cancer among older Americans, and its fundamental molecular causes were showcased during a session of insightful talks by thought leaders in cancer research at the recent SWCRF Breakthroughs 2015 Scientific Review and Symposium presented by the Samuel Waxman Cancer Research Foundation (SWCRF). The annual event brings together leading cancer scientists who present updates on their research projects funded by the SWCRF.
“The quality of the science presented at our SWCRF Breakthroughs review was nothing short of outstanding,” said Samuel Waxman, M.D., founder and CEO of the Samuel Waxman Cancer Research Foundation. “From immunotherapy to autophagy to stem cell research, our funded investigators are working on the cutting edge of state-of-the-art science to reprogram cancer cells and they’re producing clinical trials showing hopeful early patient outcomes.”
|Jonathan Licht, MD, Siddhartha Mukherjee, MD, PhD, Samuel Waxman, MD, Robert A. Weinberg, PhD and Alan Rosmarin, MD|
Held on May 3 and 4 at the Leon and Norma Hess Center for Science and Medicine at the Icahn School of Medicine at Mount Sinai, the event also recognized the contributions of two celebrated cancer researchers --- Siddhartha Mukherjee, M.D., Ph.D., of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, and Robert A. Weinberg, Ph.D., Founding Member of the Whitehead Institute for Biomedical Research.
Dr. Mukherjee, whose book The Emperor of All Maladies: A Biography of Cancer, won a 2011 Pulitzer Prize and inspired the recent PBS documentary “Cancer: The Emperor of All Maladies,” received the SWCRF Distinguished Service Award for generating widespread public interest in cancer research through his published work.
Dr. Weinberg, a longtime SWCRF collaborator, received the SWCRF Lifetime Achievement in Science Award for his contributions to cancer research, including his isolation of the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene.
The two-day event highlighted the transformative impact of cross-institutional scientific collaboration that is the hallmark of the SWCRF grant process, which requires that grantees partner across NCI-designated research facilities on projects to receive funding. SWCRF-funded investigators hail from the world’s leading research institutes, including Dana-Farber Cancer Institute, Johns Hopkins University, Memorial Sloan-Kettering Cancer Center, Icahn School of Medicine at Mount Sinai, Sheba Medical Center, the Shanghai Institute of Hematology and Weill Cornell Medical Center, among many others.
|Jonathan Licht, MD, Lorraine Gudas, PhD, Steven Gore, MD, Hua Yu, PhD and Alan Rosmarin, MD|
This year’s review was led by SWCRF scientific leaders Dr. Waxman, SWCRF Chief Scientific Officer Jonathan Licht, M.D., and Chief Mission Officer Alan Rosmarin, M.D.
The researchers’ progress reports were reviewed by the distinguished members of the SWCRF Scientific Advisory Board, which includes Steven Gore, M.D., Yale University; Lorraine Gudas, Ph.D., Weill Cornell Medical Center; Ramon Parsons, M.D., Ph.D., Icahn School of Medicine; Nancy Speck, Ph.D., University of Pennsylvania; and Hua Yu, Ph.D., City of Hope.
Contemplating Aging and Cancer
The brainstorming session on Aging and Cancer, moderated by Dr. Licht, assembled an impressive roster of SWCRF-funded scientists as a prelude to discussions of a new category of funded investigation proposed by the SWCRF scientific leadership.
The talks included:
Clonal Hematopoiesis, Aging and Leukemia by Ross Levine, MD, Memorial Sloan Kettering who described his recent findings of premalignant molecular changes in apparently normal aging individuals that set the stage for later development of leukemias and other cancers.
Cancer Biology, Aging and Tumor Dissemination discussed by Robert Weinberg, PhD, Whitehead Institute/MIT described fundamental changes in the biology of cancer cells that resemble aspects of embryonic development, and may provide new tools against the development of cancer progression and metastasis.
Cancer Metabolism, Aging and Cancer by Ron Evans, PhD, Salk Institute, who addressed the increasingly important interactions of key vitamins and the immune system in cancer development and progression.
The Aging Epigenome and Cancer by Stephen Baylin, MD, Johns Hopkins School of Medicine addressed alterations in epigenetics – modifications of DNA and the proteins that support it – and how this may be manipulated to induce immune responses against cancer.
The NASA Genome Epigenome Project by guest speaker Chris Mason, PhD, Weill Cornell Medical College, who outlined a one-year research project examining the genetic affects of space flight – including its impact on aging - by studying a set of famous twins – astronaut Scott Kelly, who is currently in space, and his brother, retired astronaut Mark Kelly, who will remain on Earth for the duration of the project.
Progress in Funded Investigations
Presentations by current grantees during the Breakthroughs portion of the review revealed significant progress in SWCRF-funded projects, including new discoveries in understanding transcription factors and DNA modifications that promote cancers – documented by leading peer-reviewed cancer journals – and potential patient treatments being tested in clinical trials.
Differentiation of the cancer cell through the targeting of mutations and epigenetic changes was a theme that was addressed in many of the presentations. The team led by Dr. Yang Shi of Boston Children’s Hospital/Harvard Medical School is attempting to extend the benefits of retinoic acid, the therapeutic agent successfully applied to APL in combination with arsenic trioxide by Dr. Waxman and his colleagues at the Shanghai Institute of Hematology (SIH), to other leukemia types. The SIH is currently investigating how a protein called RIG-I can restrain the cancer-promoting signaling of a pathway known as P13K/AKT. Collaborators Brad Cairns, Ph.D., University of Utah, and David Jones, Ph.D., Oklahoma Medical Center, showed how retinoic acid controls the rate of proliferation of intestinal cells in part by altering cell metabolism.
Exciting new clinical trials were shared by several reporting teams. Dr. Levine’s work showing how mutations in the TET2 gene accelerate the onset of AML has produced a trial at Memorial Sloan Kettering for a therapy that blocks the mutation, reprogramming the cells of several patients to normal. Drs. Ethan Dmitrovsky, Provost of MD Anderson Cancer Center, and Duane Compton of Dartmouth Medical School are using drug combinations that target chromosome instability in lung cancer therapy and their theories have led to a successful series of clinical trials for new chemical inhibitors of this pathway. Immunotherapy enhanced by DNA reprogramming is the work of the SWCRF-funded team at Johns Hopkins, Drs. Steven Baylin, Robert Casero and Cynthia Zahnow, which was published in the journal Oncotarget last year and has progressed to a Phase 2 trial for potential inhibitors of cancer-causing mutations that alter DNA. Dr. Licht and his collaborator Wilson Miller, M.D., Ph.D., of the Jewish General Hospital, are targeting histone methylation ---- a process critical for the regulation of gene expression --- with a clinical trial involving the HDAC enzyme inhibitor Panobinostat.
The complete agenda of presentations and speakers included:
Reports from the newest SWCRF grantees
Epigenetic Regulators of Differentiation in AML by Andres Blanco, PhD, representing principal investigator Yang Shi, PhD of Boston Children’s Hospital
Autophagy and Cancer by Jay Debnath, PhD, University of California San Francisco
Epigenetics and Pancreatic Cancer by Gregory David, PhD, New York University
Update from the Shanghai Institute of Hematology
Targeting Mutations of the DDX3X gene by Lu Jiang, Shanghai Institute of Hematology
Therapeutic Targets I – moderated by Jonathan Licht, M.D.
Targeting Tumor Dormancy by Julio Aguirre-Ghiso, PhD, Icahn School of Medicine at Mount Sinai
Targeting Transcription Factors by Ari Melnick, MD, Weill Cornell, in collaboration with Alex MacKerrel,PhD, University of Maryland and Gilbert Prive, PhD, Ontario Cancer Institute
Targeting Brain Tumors by William Weiss, MD, PhD, University of California San Francisco and Kevan Shokat, PhD, and Albert Baldwin, PhD, University of North Carolina
Targeting the Epigenome in Colon Cancer by David Jones, PhD, Oklahoma Medical Center and Bradley Cairns, PhD, University of Utah
Targeting the Cell Cycle in Lung Cancer by Ethan Dmitrovsky, MD, Provost of MD Anderson Cancer Center
Stem Cell and Therapeutic Targeting II - moderated by Dr. Alan Rosmarin
CML and Stem Cells by Ravi Bhatia, MD, University of Alabama and Yongkui Jing, PhD, Icahn School of Medicine at Mount Sinai
Therapeutic Targeting of the Malignant Platelet Precursor by John Crispino, PhD, Northwestern University and Shai Izraeli, MD, Sheba Medical Center, Tel Hashomer
DNMT3A, Stem Cell Function and Leukemia by Peggy Goodell, PhD, Baylor College of Medicine
C/EBPs, Stem Cells and Leukemia by Alan Friedman, MD, Johns Hopkins School of Medicine
Epigenetic Reprogramming for an Enhanced Immune Response in Cancer by Robert Casero Jr., PhD, and Cynthia Zahnow, PhD, Johns Hopkins School of Medicine
Dysregulation of TET DNA dioxygenases in AML by Yue Xiong, PhD, University of North Carolina, Chapel Hill
Therapeutic targets III – moderated by Ethan Dmitrovsky, MD
Modulating Sin3a Function for Epigenetic Therapy by Samuel Waxman, MD, Ming Ming Zhou, PhD, Icahn School of Medicine at Mount Sinai and Arthur Zelent, PhD, University of Miami
Small Molecule Inhibitors of Cancer Invasion and Metastasis by Paul Fisher, M.Ph., PhD, Virginia Commonwealth University
Update on BRD4 Therapy by Chris French, MD, PhD, Brigham and Women’s Hospital, in collaboration with Jay Bradner, MD, Dana Farber Cancer Institute
Targeting Histone Methylation by Jonathan Licht, MD, Northwestern University, and Wilson Miller MD, PhD, McGill University
Targeting Liver Cancer by Josep Llovet, MD, Icahn School of Medicine at Mount Sinai
Exploring the Role of the Mitochondrial UPR in Aging and Cancer by Doris Germain, PhD, Icahn School of Medicine at Mount Sinai
Targeting EWS/FLI-1 by Erwin Van Meir, PhD, Emory University
To view a gallery of photos from the event, click here.
For more details on our researchers' funded projects, click here.
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