Frederick W. Alt, PhD, Honored with 2021 AACR Award for Lifetime Achievement in Cancer Research

PHILADELPHIA — The American Association for Cancer Research (AACR) is recognizing highly accomplished geneticist Frederick W. Alt, PhD, with the 18th AACR Award for Lifetime Achievement in Cancer Research.

Alt is a Howard Hughes Medical Institute investigator, director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, and the Charles A. Janeway Professor of Pediatrics and a professor of genetics at Harvard Medical School. He is being honored for his discovery of gene amplification in mammalian cancer cells. His research established oncogene amplification as a mechanism of tumor progression and elucidated non-homologous DNA end joining, a pathway that repairs double-strand breaks in DNA. His findings have revolutionized scientific understanding of how genomic rearrangements occur and how they contribute to cancer.

“Dr. Alt is a pioneer in the fields of genetics and immunology whose landmark discoveries have had a defining impact on the study of cancer biology,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “We thank him for his immeasurable contributions to cancer research and are proud to honor his ongoing dedication to progress against cancer with this award.”

The AACR Award for Lifetime Achievement in Cancer Research was established in 2004 to honor individuals who have made significant fundamental contributions to cancer research, either through a single scientific discovery or a collective body of work. These contributions, whether in research, leadership, or mentorship, must have had a lasting impact on the cancer field and must have demonstrated a lifetime commitment to progress against cancer.

Early in his career, Alt made a landmark discovery that would have a far-reaching and long-lasting impact on the cancer biology field. His discovery of dihydrofolate reductase (DHFR) gene amplification provided the first molecular demonstration of genomic instability in mammalian cancer cells. His work also provided a molecular basis for considering cancer genomes as distinctly different from normal cell genomes. His subsequent discovery of N-myc, based on observed amplification rates in human neuroblastomas, was critical in establishing oncogene amplification as a fundamental tumor-progression mechanism and provided several examples of cancer genomic instability. His discoveries revealed both a mechanism for how cancer cells acquire drug resistance and a mechanism for how they develop more potent oncogenes.

Alt’s later discovery of key non-homologous DNA end joining, one of the two major mammalian DNA double-strand break repair pathways, played a major part in establishing its critical role in suppressing the rearrangements and amplifications that cause cancer. Building upon this discovery, Alt demonstrated alternative end-joining pathways and described their role in mediating chromosomal translocations.

Throughout his career, Alt has mentored over 150 students and research fellows, many of who have gone on to become prominent cancer researchers and leaders in the fields of immunology, genetics, and cancer biology. 

An AACR member since 1989, Alt received the AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research in 2004. He previously served the AACR as a member of the AACR Award for Lifetime Achievement in Cancer Research Committee from 2018-2020, the AACR Nominating Committee from 2016-2018, the AACR-Cancer Research Institute Lloyd J. Old Award in Cancer Immunology Committee from 2015-2017, and as a member of the AACR Laboratory Research Awards Committee from 2012-2014.

Alt was elected to the National Academy of Medicine and the American Association for the Advancement of Science in 2011, and to the American Academy of Microbiology, the U.S. National Academy of Sciences, and the American Academy of Arts and Sciences in 1994. He received the National Institutes of Health Merit Award twice (2019 and 1991); the American Association of Immunologists AAI-BioLegend Herzenberg Award (2019); the William Silen Lifetime Achievement Excellence in Mentoring Award (2016); the American-Italian Cancer Foundation Prize for Scientific Excellence in Medicine (2015); the Katharine Berkan Judd Award for Distinguished Achievement in Biomedical Research (2015); the National Foundation for Cancer Research Szent-György Prize for Progress in Cancer Research (2015); the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science (2015); the Stanford University Medical Center Arthur Kornberg and Paul Berg Lifetime Achievement Award in Biomedical Science (2012); the Cancer Research Institute William B. Coley Award for Distinguished Research in Basic Immunology (2009); the Novartis Prize for Basic Immunology (2007); the American Association of Immunologists AAI-Huang Foundation Meritorious Career Award (2007); the Alfred K. Knudson Award (2007); the Pasarow Foundation Prize for Extraordinary Achievement in Cancer Research (2005); the Leukemia and Lymphoma Society de Villiers International Achievement Award (2005); the Rabbi Shai Shacknai Memorial Prize in Immunology and Cancer Research (2005); the Irvington Institute Scientific Leadership Award in Immunology (2005); the American Association of immunologists Excellence in Mentoring Award (2003); the Mallinckrodt Award (1984); and the Irma T. Hirschl Career Scientist Award (1983).

Alt received his doctorate in biology from Stanford University in 1977 and did his postdoctoral training at the Massachusetts Institute of Technology with Nobel Laureate David Baltimore, PhD.