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Therapy-induced senescence: opportunities to improve anti-cancer therapy

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Item Type:Review
Title:Therapy-induced senescence: opportunities to improve anti-cancer therapy
Creators Name:Prasanna, P.G. and Citrin, D.E. and Hildesheim, J. and Ahmed, M.M. and Venkatachalam, S. and Riscuta, G. and Xi, D. and Zheng, G. and van Deursen, J. and Goronzy, J. and Kron, S.J. and Anscher, M.S. and Sharpless, N.E. and Campisi, J. and Brown, S.L. and Niedernhofer, L.J. and O'Loghlen, A. and Georgakilas, A.G. and Paris, F. and Gius, D. and Gewirtz, D.A. and Schmitt, C.A. and Abazeed, M.E. and Kirkland, J.L. and Richmond, A. and Romesser, P.B. and Lowe, S.W. and Gil, J. and Mendonca, M.S. and Burma, S. and Zhou, D. and Coleman, C.N.
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.
Keywords:Cancer, Cancer Therapy, Radiation, Radiation Therapy, Senescence, Aging, "One-Two Punch" Cancer Therapy, Therapy-Induced Senescence, Senotherapeutics, Senolytics, Senomorphics
Source:Journal of the National Cancer Institute
ISSN:0027-8874
Publisher:Oxford University Press
Page Range:djab064
Date:1 April 2021
Official Publication:https://doi.org/10.1093/jnci/djab064
PubMed:View item in PubMed

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