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: Thomas W Kensler, Avrum Spira, Judy E Garber, Eva Szabo, J Jack Lee, Zigang Dong, Andrew J Dannenberg, William N Hait, Elizabeth Blackburn, Nancy E Davidson, Margaret Foti, Scott M Lippman
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 9 Issue 1 Pg. 2-10 (Jan 2016) ISSN: 1940-6215 [Electronic] United States
• PMID: 26744449 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Cancer Vaccines
• Immunosuppressive Agents

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Biopsy
• Cancer Vaccines
• Disease Progression
• Female
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• Immune System
• Immunosuppressive Agents (therapeutic use)
• Male
• Mice
• Neoplasms (immunology, prevention & control)
• Precancerous Conditions (pathology)
• Precision Medicine (methods)
• Randomized Controlled Trials as Topic
• Sequence Analysis, DNA
• Tumor Microenvironment