Leveraging premalignant biology for immune-based cancer prevention

Avrum Spira, Mary L. Disis, John T. Schiller, Eduardo Vilar, Timothy R. Rebbeck, Rafael Bejar, Trey Ideker, Janine Arts, Matthew B. Yurgelun, Jill P. Mesirov, Anjana Rao, Judy Garber, Elizabeth M. Jaffee, Scott M. Lippman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)10750-10758
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
StatePublished - Sep 27 2016


  • Biology
  • Cancer prevention
  • Immune oncology
  • Premalignancy
  • Vaccines

ASJC Scopus subject areas

  • General


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