TY - JOUR
T1 - Therapy-Induced Senescence
T2 - Opportunities to Improve Anticancer Therapy
AU - Prasanna, Pataje G.
AU - Citrin, Deborah E.
AU - Hildesheim, Jeffrey
AU - Ahmed, Mansoor M.
AU - Venkatachalam, Sundar
AU - Riscuta, Gabriela
AU - Xi, Dan
AU - Zheng, Guangrong
AU - Deursen, Jan van
AU - Goronzy, Jorg
AU - Kron, Stephen J.
AU - Anscher, Mitchell S.
AU - Sharpless, Norman E.
AU - Campisi, Judith
AU - Brown, Stephen L.
AU - Niedernhofer, Laura J.
AU - O'loghlen, Ana
AU - Georgakilas, Alexandros G.
AU - Paris, Francois
AU - Gius, David
AU - Gewirtz, David A.
AU - Schmitt, Clemens A.
AU - Abazeed, Mohamed E.
AU - Kirkland, James L.
AU - Richmond, Ann
AU - Romesser, Paul B.
AU - Lowe, Scott W.
AU - Gil, Jesus
AU - Mendonca, Marc S.
AU - Burma, Sandeep
AU - Zhou, Daohong
AU - Coleman, C. Norman
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/djab064
DO - 10.1093/jnci/djab064
M3 - Review article
C2 - 33792717
AN - SCOPUS:85105534111
SN - 0027-8874
VL - 113
SP - 1285
EP - 1298
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 10
ER -