The senescence-associated secretory phenotype in ovarian cancer dissemination

Am J Physiol Cell Physiol. 2022 Jul 1;323(1):C125-C132. doi: 10.1152/ajpcell.00049.2022. Epub 2022 May 18.

Abstract

Ovarian cancer is a highly aggressive disease with poor survival rates in part due to diagnosis after dissemination throughout the peritoneal cavity. It is well-known that inflammatory signals affect ovarian cancer dissemination. Inflammation is a hallmark of cellular senescence, a stable cell cycle arrest induced by a variety of stimuli including many of the therapies used to treat patients with ovarian cancer. Indeed, recent work has illustrated that ovarian cancer cells in vitro, mouse models, and patient tumors undergo senescence in response to platinum-based or poly(ADP-ribose) polymerase (PARP) inhibitor therapies, standard-of-care therapies for ovarian cancer. This inflammatory response, termed the senescence-associated secretory phenotype (SASP), is highly dynamic and has pleiotropic roles that can be both beneficial and detrimental in cell-intrinsic and cell-extrinsic ways. Recent data on other cancer types suggest that the SASP promotes metastasis. Here, we outline what is known about the SASP in ovarian cancer and discuss both how the SASP may promote ovarian cancer dissemination and strategies to mitigate the effects of the SASP.

Keywords: disease progression; metastasis; microenvironment; secretome; therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • Cellular Senescence
  • Female
  • Humans
  • Mice
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Phenotype
  • Poly(ADP-ribose) Polymerases / genetics
  • Senescence-Associated Secretory Phenotype*

Substances

  • Poly(ADP-ribose) Polymerases