title: Transforming Cancer Prevention through Precision Medicine and Immune-oncology.
abstract: We have entered a transformative period in cancer prevention (including early detection). Remarkable progress in precision medicine and immune-oncology, driven by extraordinary recent advances in genome-wide sequencing, big-data analytics, blood-based technologies, and deep understanding of the tumor immune microenvironment (TME), has provided unprecedented possibilities to study the biology of premalignancy. The pace of research and discovery in precision medicine and immunoprevention has been astonishing and includes the following clinical firsts reported in 2015: driver mutations detected in circulating cell-free DNA in patients with premalignant lesions (lung); clonal hematopoiesis shown to be a premalignant state; molecular selection in chemoprevention randomized controlled trial (RCT; oral); striking efficacy in RCT of combination chemoprevention targeting signaling pathway alterations mechanistically linked to germline mutation (duodenum); molecular markers for early detection validated for lung cancer and showing promise for pancreatic, liver, and ovarian cancer. Identification of HPV as the essential cause of a major global cancer burden, including HPV16 as the single driver of an epidemic of oropharyngeal cancer in men, provides unique opportunities for the dissemination and implementation of public health interventions. Important to immunoprevention beyond viral vaccines, genetic drivers of premalignant progression were associated with increasing immunosuppressive TME; and Kras vaccine efficacy in pancreas genetically engineered mouse (GEM) model required an inhibitory adjuvant (Treg depletion). In addition to developing new (e.g., epigenetic) TME regulators, recent mechanistic studies of repurposed drugs (aspirin, metformin, and tamoxifen) have identified potent immune activity. Just as precision medicine and immune-oncology are revolutionizing cancer therapy, these approaches are transforming cancer prevention. Here, we set out a brief agenda for the immediate future of cancer prevention research (including a "Pre-Cancer Genome Atlas" or "PCGA"), which will involve the inter-related fields of precision medicine and immunoprevention - pivotal elements of a broader domain of personalized public health.
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.affiliation: Boston University, Boston, Massachusetts.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Weill Cornell Medical College, New York, New York.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: William N
authors.initials: WN
authors.lastname: Hait
authors.affiliation: Salk Institute for Biological Studies, La Jolla, California.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Blackburn
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.affiliation: American Association for Cancer Research, Philadelphia, Pennsylvania.
authors.forename: Margaret
authors.initials: M
authors.lastname: Foti
authors.affiliation: Moores Cancer Center, University of California San Diego, La Jolla, California. slippman@ucsd.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D019496:Cancer Vaccines; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007107:Immune System; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000473:pathology; D057285:Precision Medicine / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D017422:Sequence Analysis, DNA; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D007166:Immunosuppressive Agents