Liang Yabing, Wang Miao, Wang Xianjue, Yang Zhiqing, Wang Shucheng, Li Fengyi, Su Liya, Yang Ling
Key Laboratory of Medical Cell Biology in Inner Mongolia, Clinical Medicine Research Center, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, China.
Front Oncol. 2025 Aug 15;15:1580951. doi: 10.3389/fonc.2025.1580951. eCollection 2025.
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Although the use of small molecule drugs or targeted drugs has shown significant efficacy in the treatment of CRC, the drug resistance after treatment and the high recurrence and metastasis rate are the key obstacles affecting the success rate of treatment and survival of patients. Cellular senescence constitutes an important barrier to tumor progression. Senescent tumor cells and stromal cells are among the reasons for cancer treatment resistance. Different senescent programs can exert inhibitory or promotional effects on CRC. In serrated adenomas of colon, the senescence induced by intrinsic oncogenes serves as a threshold that precancerous lesions must traverse to develop into cancer. And the exposing of anti-cancer treatment, such as chemotherapy and radiotherapy, some cells also enter a senescent state, presenting a stable cell cycle arrest and senescence-associated secretory phenotype (SASP). SASP can activate immune surveillance but also contribute to the maintenance of cellular senescence microenvironment to help the CRC progression. Hence, in the pursuit of effective CRC treatment strategies, the issue of senescent cells is inevitable. By targeting features of senescent cells, such as upregulated anti-apoptotic signaling, altered metabolic signaling, and differential SASP secretion, depletion of senescent cells could be a promising strategy for the treatment of CRC. This review summarizes the endogenous and exogenous factors leading to cell senescence in CRC, as well as drug mechanisms, and focuses on the research progress of senescent tumors and stromal cells in CRC. Eventually, we discuss the strategies for CRC senescent cells after anti-cancer treatment to provide some theoretical basis and direction for retarding the malignant progression and recurrence of CRC.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一。尽管小分子药物或靶向药物在CRC治疗中已显示出显著疗效，但治疗后的耐药性以及高复发和转移率是影响治疗成功率和患者生存率的关键障碍。细胞衰老构成肿瘤进展的重要障碍。衰老的肿瘤细胞和基质细胞是癌症治疗耐药的原因之一。不同的衰老程序可对CRC产生抑制或促进作用。在结肠锯齿状腺瘤中，由内在癌基因诱导的衰老作为癌前病变发展为癌症必须跨越的阈值。而且，在接受化疗和放疗等抗癌治疗时，一些细胞也会进入衰老状态，表现出稳定的细胞周期停滞和衰老相关分泌表型（SASP）。SASP可激活免疫监视，但也有助于维持细胞衰老微环境以促进CRC进展。因此，在寻求有效的CRC治疗策略时，衰老细胞问题不可避免。通过靶向衰老细胞的特征，如上调的抗凋亡信号、改变的代谢信号和差异的SASP分泌，清除衰老细胞可能是一种有前景的CRC治疗策略。本综述总结了导致CRC细胞衰老的内源性和外源性因素以及药物机制，并重点关注CRC中衰老肿瘤细胞和基质细胞的研究进展。最后，我们讨论了抗癌治疗后CRC衰老细胞的应对策略，为延缓CRC的恶性进展和复发提供一些理论依据和方向。
