Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy

Pataje G. Prasanna*, Deborah E. Citrin, Jeffrey Hildesheim, Mansoor M. Ahmed, Sundar Venkatachalam, Gabriela Riscuta, Dan Xi, Guangrong Zheng, Jan van Deursen, Jorg Goronzy, Stephen J. Kron, Mitchell S. Anscher, Norman E. Sharpless, Judith Campisi, Stephen L. Brown, Laura J. Niedernhofer, Ana O'loghlen, Alexandros G. Georgakilas, Francois Paris, David R GiusDavid A. Gewirtz, Clemens A. Schmitt, Mohamed E. Abazeed, James L. Kirkland, Ann Richmond, Paul B. Romesser, Scott W. Lowe, Jesus Gil, Marc S. Mendonca, Sandeep Burma, Daohong Zhou, C. Norman Coleman

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations

Abstract

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction of tumor cell senescence is also one of the underlying mechanisms by which cancer therapies exert antitumor activity. However, an increasing body of evidence from preclinical studies demonstrates that radiation and chemotherapy cause accumulation of senescent cells (SnCs) both in tumor and normal tissue. SnCs in tumors can, paradoxically, promote tumor relapse, metastasis, and resistance to therapy, in part, through expression of the senescence-associated secretory phenotype. In addition, SnCs in normal tissue can contribute to certain radiation- A nd chemotherapy-induced side effects. Because of its multiple roles, cellular senescence could serve as an important target in the fight against cancer. This commentary provides a summary of the discussion at the National Cancer Institute Workshop on Radiation, Senescence, and Cancer (August 10-11, 2020, National Cancer Institute, Bethesda, MD) regarding the current status of senescence research, heterogeneity of therapy-induced senescence, current status of senotherapeutics and molecular biomarkers, a concept of "one-two punch"cancer therapy (consisting of therapeutics to induce tumor cell senescence followed by selective clearance of SnCs), and its integration with personalized adaptive tumor therapy. It also identifies key knowledge gaps and outlines future directions in this emerging field to improve treatment outcomes for cancer patients.

Original languageEnglish (US)
Pages (from-to)1285-1298
Number of pages14
JournalJournal of the National Cancer Institute
Volume113
Issue number10
DOIs
StatePublished - Oct 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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