Frederick Alt, HMS professor of genetics, director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, and Howard Hughes Medical Institute Investigator, has been awarded the 2015 Szent-Györgyi Prize for Progress in Cancer Research by the National Foundation for Cancer Research.
Alt’s groundbreaking work in cancer genetics over four decades has helped to shape the very roots of modern cancer research and continues to impact the approaches that doctors use to diagnose and treat cancer.
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The selection committee was unanimous in its decision to recognize Alt, whose work has proved fundamental to the modern understanding of cancer—not only how the lethal disease forms, but also how it can become resistant to treatment.
In particular, his seminal discoveries of gene amplification and his pioneering work on molecular mechanisms of DNA-damage repair have helped to usher in the era of genetically targeted therapy and personalized medicine.
“Dr. Alt has been a consistently outstanding scientist throughout his career, and this award recognizes his entire body of work,” said James Allison, executive director of the immunotherapy platform at the University of Texas MD Anderson Cancer Center, winner of the 2014 Szent-Györgyi Prize and chair of this year’s prize selection committee. “The genetic processes he described are central to understanding the mechanisms that cause cancer and have ultimately led to an entire class of targeted therapy and associated diagnostics that are providing benefit to countless cancer patients.”
Alt’s discovery of gene amplification in chemotherapy-resistant cancer cells—which revealed that cells can produce multiple copies of a gene—was revolutionary, coming at a time when the human genome was widely believed to be stable and inflexible.
This radical concept suggested that cancer cells could change their genes, a process that would both allow the cells to develop more potent cancer-causing genes as well as evolve resistance to treatment.
Alt, who is also the HMS Charles A. Janeway Professor of Pediatrics at Boston Children’s, proved the generality of his initial discoveries when he showed that the gene n-myc is commonly amplified in the childhood cancer neuroblastoma. Today, genomic instability is recognized as one of the hallmarks of cancer.
Equally important is Alt’s work on the critical DNA-repair mechanism called non-homologous end joining (NHEJ). Alt not only made the initial experimental findings that led to the discovery of this pathway but also carried out an ingenious series of experiments over many years in his lab, taking it apart piece by piece to understand how it works. This work linked NHEJ to protecting against a specific kind of DNA damage called translocations, which is a major component of many cancers, especially leukemia and lymphoma.
Both amplified genes and translocated genes are key components of the precision medicine paradigm, which is at the heart of 21st century medicine. By identifying the source of genetic abnormalities that drive both cancer development and drug resistance, Alt’s insights helped to revolutionize cancer diagnostics and treatment. His discoveries led to a wholly new approach to treating cancer—identifying these genetic abnormalities then selecting new drugs that target each specifically.
“I am truly honored to be selected by the National Foundation for Cancer Research to receive this award, and I am humbled to stand with past winners of the Szent-Györgyi Prize.” said Alt. “Cancer is a complex and terrible disease, but with each new discovery we are making it less mysterious, more understandable and ultimately less deadly. We are making progress.”
“Dr. Alt’s work has uncovered and explained some of the most foundational chemistry of life, and throughout his career he has always been focused on the implications for cancer. His vision and talent were instrumental in bringing cancer research into the modern era, and we are proud to present him with this award,” said Sujuan Ba, co-chair of the 2015 Szent-Györgyi Prize selection committee and president of NFCR.
The Szent-Györgyi Prize for Progress in Cancer Research was established by the National Foundation for Cancer Research in honor of Albert Szent-Györgyi, its co-founder and recipient of the 1937 Nobel Prize for Physiology and Medicine.
Dr. Alt has won numerous honors for biomedical research, including the Stanford University Medical Center Alumni Association Arthur Kornberg and Paul Berg Lifetime Achievement Award in Biomedical Science, and the National Cancer Institute Alfred G. Knudson Award for Excellence in Cancer Genetics. Each year the Cancer Research Institute of New York presents the Frederick W. Alt Award for New Discoveries in Cancer Immunology in his honor.
Dr. Alt’s impact extends far beyond his own laboratory. An outstanding researcher, he is also an exemplary teacher. In 2003 he received the American Association of Immunologists Excellence in Mentoring Award. Dr. Alt has mentored more than 100 students and research fellows, many of whom have become leaders in immunology, genetics or cancer biology.
