Deregulation of Retroelements as an Emerging Therapeutic Opportunity in Cancer

Trends Cancer. 2018 Aug;4(8):583-597. doi: 10.1016/j.trecan.2018.05.008. Epub 2018 Jun 19.

Abstract

Nearly half of the human genome is comprised of repetitive elements that are tightly regulated to protect the host genome from deleterious consequences associated with their inappropriate activation. Cancer cells often misexpress these elements, in part, due to decreases in DNA methylation. Recent discoveries suggest that tumor suppressor proteins contribute to repression of repetitive elements, and their functional inactivation promotes repeat element misexpression during carcinogenesis. Recent findings also suggest that increased expression of repetitive elements beyond a threshold of tolerance can augment cancer therapy responses. Such advances, reviewed here, paint a picture in which deregulated expression of repetitive genome elements not only contributes to the development of cancer but may also provide a tumor-specific Achilles heel for cancer treatment.

Keywords: endogenous retroviruses; immunotherapy; repetitive elements; viral mimicry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Humans
  • Neoplasms / genetics*
  • Retroelements*

Substances

  • Antigens, Neoplasm
  • Heterochromatin
  • Retroelements