Leveraging premalignant biology for immune-based cancer prevention
Abstract
Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system’s ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 16, 2016
- Source ID
- 10.1073/pnas.1608077113
Entities
People
- Anjana Rao
- Avrum Spira
- Eduardo Vilar
- Elizabeth M. Jaffee
- Janine Arts
- Jill P. Mesirov
- John T. Schiller
- Judy Garber
- Mary L. Disis
- Matthew B. Yurgelun
- Rafael Bejar
- Scott M. Lippman
- Timothy R Rebbeck
- Trey Ideker
Organizations
- Boston University
- Center for Cancer Research
- Dana–Farber Cancer Institute
- La Jolla Institute for Allergy and Immunology
- National Cancer Institute
- Sidney Kimmel Comprehensive Cancer Center
- United States Department of Defense
- University of California, San Diego
- University of Texas at Austin
- University of Washington