Interactions between oxidative stress and senescence in cancer: Mechanisms, therapeutic implications, and future perspectives

Abstract

Background: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved.

Aim: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects.

Methods: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked.

Results: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP.

Concludsion: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.

Keywords: Aging; Cancer; Oxidative stress; SASP; Senescence.

Fig. 1

The regulatory network of oxidative stress and senescence in carcinogenesis: life habits, drugs, targeting genes and pathways (including the NRF2 and STAT3 pathways) could generate oxidative stress-induce senescent cells to prevent tumorigenesis. SASP secreted by senescent cells promoted tumorigenesis. ROS: reactive oxidative species; H2O2: hydrogen peroxide; SASP: senescence-associated secretory phenotype.

Fig. 2

The regulatory network of oxidative stress and senescence in cancer progression: the suppression of cancer progression can be achieved by targeting specific genes or pathways that promote oxidative stress-induced cellular senescence. CAFs generated SASP to promote cancer progression. Interestingly, cancer cells could also enhance the ROS level of CAFs. ROS: reactive oxidative species; H2O2: hydrogen peroxide; SASP: senescence-associated secretory phenotype; CAF: cancer-associated fibroblast.

Fig. 3

The regulatory network of oxidative stress and senescence in therapy resistance: many current clinical therapies combine with novel drugs to overcome resistance and alleviate side effects by attenuating oxidative stress-induced cellar senescence. SASP is a mainly transport way to contact cancer cells and stromal cells. ROS: reactive oxidative species; H2O2: hydrogen peroxide; SASP: senescence-associated secretory phenotype.

Fig. 4

The regulatory network of oxidative stress and senescence in emerging drugs: emerging drugs, including natural products and other compounds, are being investigated for their ability to control cancer development by enhancing oxidative stress-induced cellular senescence. These drugs could affect both cancer cell and SASP. ROS: reactive oxidative species; H2O2: hydrogen peroxide; SASP: senescence-associated secretory phenotype.