Cellular senescence: a promising strategy for cancer therapy

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.

Role of p53 in the Regulation of Cellular Senescence

“…It was reported that reactivation of p53 in tumors provokes tumor regression mediated by induction of senescence [103]. Moreover, small molecules were developed to increase the amount or the activity of p53 in cancer cells [104]. For example, Nutlin stabilizes p53 by inhibiting p53 interactions with MDM2 [105].…”

“…For example, Nutlin stabilizes p53 by inhibiting p53 interactions with MDM2 [105]. Another study reported that the inhibition of the interaction between p53 and MDM4, a negative regulator of p53, restores the activity of p53 in melanoma cells, resulting in an increased sensitivity to cytostatic or cytotoxic therapy [104]. The idea of reactivating p53 to reduce the tumor progression is very appealing, and many therapeutic strategies have been under study.…”

“…The downside of this senescence-inducing approach is that senescent cells often align with malignant cells and support tumor expansion [104] as well as cancer initiation and progression [107]. Senescent cells regulate tumorigenesis and the immune response of their neighbors in both a positive and a negative manner via SASP and depending on the genetic context, thus limiting the application of this therapy [104].…”

The Plant-Derived Compound Resveratrol in Brain Cancer: A Review

“…Cellular senescence is an irreversible cell cycle arrest that is considered to be an important tumor-suppressive mechanism as it stops proliferation. Therapy-induced senescence is thought to be an effective tool in cancer treatment, with fewer side effects than apoptosis-inducing treatment [160,161]. In a study with U87 and U118 human glioma cell lines, RES inhibited proliferation by inducing cellular senescence in a dose-and time-dependent manner [162].…”

Multifaceted Roles of Caveolin-1 in Lung Cancer: A New Investigation Focused on Tumor Occurrence, Development and Therapy

“…Cell senescence refers to a physiologically inactive state and such cells undergo irreversible growth arrest [142]. Therefore, cell senescence can be regarded as a novel method of interrupting cancer cell proliferation and treating cancers [143]. In general, bleomycin can modulate Cav-1 expression, give rise to cell senescence and act as an anti-tumor agent [144].…”