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Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy

Pataje Prasanna 1 Deborah Citrin 1 Jeffrey Hildesheim 1 Mansoor Ahmed 1 Sundar Venkatachalam 1 Gabriela Riscuta 1 Dan Xi 1 Guangrong Zheng 2 Jan Van Deursen 3 Jorg Goronzy 4 Stephen Kron 5 Mitchell Anscher 6 Norman Sharpless 1 Judith Campisi 7 Stephen Brown 8 Laura Niedernhofer 9 Ana O’loghlen 10 Alexandros Georgakilas 11 Francois Paris 12 David Gius 13 David Gewirtz 14 Clemens Schmitt 15 Mohamed Abazeed 1 James Kirkland 3 Ann Richmond 16 Paul Romesser 17 Scott Lowe 17 Jesus Gil 17 Marc Mendonca 18 Sandeep Burma 19 Daohong Zhou 2 C Norman Coleman 1 
Abstract : 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.
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Pataje Prasanna, Deborah Citrin, Jeffrey Hildesheim, Mansoor Ahmed, Sundar Venkatachalam, et al.. Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy. JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), 2021, 113 (10), pp.1285-1298. ⟨10.1093/jnci/djab064⟩. ⟨inserm-03547029⟩

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