Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy

Prasanna, Pataje G, Citrin, Deborah E, Hildesheim, Jeffrey, Ahmed, Mansoor M, Venkatachalam, Sundar, Riscuta, Gabriela, Xi, Dan, Zheng, Guangrong, Deursen, Jan van, Goronzy, Jorg, Kron, Stephen J, Anscher, Mitchell S, Sharpless, Norman E, Campisi, Judith, Brown, Stephen L, Niedernhofer, Laura J, O'Loghlen, Ana, Georgakilas, Alexandros G, Paris, Francois, Gius, David, Gewirtz, David A, Schmitt, Clemens A, Abazeed, Mohamed E, Kirkland, James L, Richmond, Ann, Romesser, Paul B, Lowe, Scott W, Gil, Jesus, Mendonca, Marc S, Burma, Sandeep, Zhou, Daohong, Coleman, C Norman (October 2021) Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy. Journal of the National Cancer Institute, 113 (10). pp. 1285-1298. ISSN 0027-8874

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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- and 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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:	Lowe, Scott W.
Communities:	CSHL labs > Lowe lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	1 October 2021
Date Deposited:	13 Oct 2023 18:44
Last Modified:	25 Jan 2024 16:21
PMCID:	PMC8486333
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41273

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