BMB Reports 2019; 52(1): 35-41  
Cellular senescence: a promising strategy for cancer therapy
Seongju Lee1,2 & Jae-Seon Lee1,3,*
1Hypoxia-related Disease Research Center, 2Department of Anatomy and 3Department of Molecular Medicine, College of Medicine, Inha University, Incheon 22212, Korea
Correspondence to: Tel: +82-32-860-9832; Fax: +82-32-885-8302; E-mail: jaeslee@inha.ac.kr
Received: October 12, 2018; Published online: January 31, 2019.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
Cellular senescence, a permanent state of cell cycle arrest is believed to have originally evolved to limit the proliferation of old or damaged cells. However, it has been recently shown that cellular senescence is a physiological and pathological program contributing to embryogenesis, immune response, and wound repair, as well as aging and age-related diseases. Unlike replicative senescence associated with telomere attrition, premature senescence rapidly occurs in response to various intrinsic and extrinsic insults. Thus, cellular senescence has also been considered suppressive mechanism of tumorigenesis. Current studies have revealed that therapy-induced senescence (TIS), a type of senescence caused by traditional cancer therapy, could play a critical role in cancer treatment. In this review, we outline the key features and the molecular pathways of cellular senescence. Better understanding of cellular senescence will provide insights into the development of powerful strategies to control cellular senescence for therapeutic benefit. Lastly, we discuss existing strategies for the induction of cancer cell senescence to improve efficacy of anticancer therapy.
Keywords: Cancer therapy, Cellular senescence, Senescence features, Senescence pathways
Figures
Fig. 1. Molecular pathways of cellular senescence. DDR (DNA damage response) triggered by telomere erosion or OIS (oncogeneinduced senescence) is mediated by ATM/CHK2 and ATR/CHK1, which blocks cell cycle progression via phosphorylation and stabilization of p53. Activated p53 induces transcription of CDK inhibitor p21CIP1encoded by CDKN1A, which inhibits CDK2 activity, thereby activating RB and inducing cell cycle arrest. In parallel, various stressors also induce expression of the CDKN2A locus, which consists of p14ARF, p16INK4a, and p15INK4B. p14ARF prevents p53 destabilization by degrading the MDM2 protooncogene. Meanwhile, p16INK4a and p15INK4B suppress CDK4 and CDK6, thereby eventually activating RB. PICS (PTEN loss-induced cellular senescence) also activates p53 through the mTOR pathway. Altogether, prolonged activation of the p53/p21CIP1 and p16INK4a/RB signaling pathways leads to hypophosphorylation of RB, which blocks the cell cycle in G1 phase, and ultimately causes cellular senescence. RS and SIPS indicate replicative senescence and stress-induced premature senescence, respectively.


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