Therapy-induced senescence: opportunities to improve anti-cancer therapy
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2021-10-10
Date Acceptance
2021-03-29
Citation
Journal of the National Cancer Institute, 2021, 113 (10), pp.1285-1298
ISSN
0027-8874
Publisher
Oxford University Press
Start Page
1285
End Page
1298
Journal / Book Title
Journal of the National Cancer Institute
Volume
113
Issue
10
Copyright Statement
© The Author(s) 2021. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33792717
PII: 6207975
Subjects
"One-Two Punch" Cancer Therapy
Aging
Cancer
Cancer Therapy
Radiation
Radiation Therapy
Senescence
Senolytics
Senomorphics
Senotherapeutics
Therapy-Induced Senescence
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-04-01