细胞凋亡是由内在和外在途径介导的程序性细胞死亡的一种形式。细胞死亡的失调和抵抗是癌症的标志。三十多年来，开发通过诱导各种细胞死亡方式（包括细胞凋亡）来促进癌症治疗的疗法一直是临床肿瘤学的主要目标。细胞凋亡途径还与其他信号传导机制相互作用，例如 p53 信号传导途径和整合应激反应 (ISR) 途径。除了直接靶向内在和外在途径成分的药物外，针对 p53 和 ISR 信号途径的抗癌药物也在积极开发中。在这篇综述中，我们讨论了处于不同开发阶段的选定且有前途的抗癌疗法，包括药物靶点、机制和对相关治疗的耐药性，特别关注 B 细胞淋巴瘤 2 (BCL-2) 抑制剂、TRAIL 类似物、DR5 抗体和针对 p53、突变体 p53 和 ISR 的策略。

Apoptosis is a form of programmed cell death that is mediated by intrinsic and extrinsic pathways. Dysregulation of and resistance to cell death are hallmarks of cancer. For over three decades, the development of therapies to promote treatment of cancer by inducing various cell death modalities, including apoptosis, has been a main goal of clinical oncology. Apoptosis pathways also interact with other signaling mechanisms, such as the p53 signaling pathway and the integrated stress response (ISR) pathway. In addition to agents directly targeting the intrinsic and extrinsic pathway components, anticancer drugs that target the p53 and ISR signaling pathways are actively being developed. In this Review, we discuss selected and promising anticancer therapies in various stages of development, including drug targets, mechanisms, and resistance to related treatments, focusing especially on B cell lymphoma 2 (BCL-2) inhibitors, TRAIL analogues, DR5 antibodies, and strategies that target p53, mutant p53, and the ISR.