Cell death by apoptosis and permanent cell cycle arrest by senescence serve as barriers to the development of cancer. Chemotherapeutic agents not only induce apoptosis, they can also induce senescence known as therapy-induced senescence (TIS). There are, however, controversies whether TIS improves or worsens therapeutic outcome. Unlike apoptosis, which permanently removes cancer cells, senescent cells are metabolically active, and can contribute to tumor progression and relapse. If senescent cells are not cleared by the immune system or if cancer cells escape senescence, they may acquire resistance to apoptotic stimuli and become highly aggressive. Thus, there have been significant efforts in developing senolytics, drugs that target these pro-survival molecules to eliminate senescent cells. The anti-apoptotic Bcl-2 family proteins not only protect against cell death by apoptosis, but they also allow senescent cells to survive. While combining senolytics with chemotherapeutic drugs is an attractive approach, there are also limitations. Moreover, members of the Bcl-2 family have distinct effects on apoptosis and senescence. The purpose of this review article is to discuss recent literatures on how members of the Bcl-2 family orchestrate the interplay between apoptosis and senescence, and the challenges and progress in targeting these Bcl-2 family proteins for cancer therapy.

细胞凋亡导致的细胞死亡和衰老导致的永久细胞周期停滞是癌症发展的障碍。化学治疗剂不仅诱导细胞凋亡，它们还可以诱导衰老，称为治疗诱导的衰老 (TIS)。然而，TIS 是改善还是恶化治疗结果存在争议。与永久性去除癌细胞的细胞凋亡不同，衰老细胞具有代谢活性，可促进肿瘤进展和复发。如果衰老细胞没有被免疫系统清除或癌细胞逃脱衰老，它们可能会获得对凋亡刺激的抵抗力并变得具有高度攻击性。因此，在开发抗衰老药物方面做出了重大努力，这些药物靶向这些促生存分子以消除衰老细胞。抗凋亡 Bcl-2 家族蛋白不仅可以防止细胞因凋亡而死亡，而且它们还允许衰老细胞存活。虽然将 senolytics 与化疗药物结合是一种有吸引力的方法，但也存在局限性。此外，Bcl-2 家族的成员对细胞凋亡和衰老有明显的影响。这篇评论文章的目的是讨论最近关于 Bcl-2 家族成员如何协调细胞凋亡和衰老之间相互作用的文献，以及将这些 Bcl-2 家族蛋白靶向用于癌症治疗的挑战和进展。Bcl-2 家族的成员对细胞凋亡和衰老具有不同的影响。这篇评论文章的目的是讨论最近关于 Bcl-2 家族成员如何协调细胞凋亡和衰老之间相互作用的文献，以及将这些 Bcl-2 家族蛋白靶向用于癌症治疗的挑战和进展。Bcl-2 家族的成员对细胞凋亡和衰老具有不同的影响。这篇评论文章的目的是讨论最近关于 Bcl-2 家族成员如何协调细胞凋亡和衰老之间相互作用的文献，以及将这些 Bcl-2 家族蛋白靶向用于癌症治疗的挑战和进展。