Targeting apoptotic pathways for cancer therapy

• Published in: The Journal of clinical investigation 2024-07, Vol.134 (14), p.1-12
• Main Authors: Tian, Xiaobing, Srinivasan, Praveen R, Tajiknia, Vida, Sanchez Sevilla Uruchurtu, Ashley F, Seyhan, Attila A, Carneiro, Benedito A, De La Cruz, Arielle, Pinho-Schwermann, Maximilian, George, Andrew, Zhao, Shuai, Strandberg, Jillian, Di Cristofano, Francesca, Zhang, Shengliang, Zhou, Lanlan, Raufi, Alexander G, Navaraj, Arunasalam, Zhang, Yiqun, Verovkina, Nataliia, Ghandali, Maryam, Ryspayeva, Dinara, El-Deiry, Wafik S
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic drugs; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; Cancer; Cancer therapies; Care and treatment; Cell death; Cellular stress response; Chemotherapy; Competition; Cytochrome; Development and progression; Drug delivery; Drug development; FDA approval; Health aspects; Humans; Leukemia; Lymphoma; Molecular targeted therapy; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Oncology, Experimental; Pancreatic cancer; Polyethylene glycol; Proteins; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Review; Signal transduction; Signal Transduction - drug effects; Therapeutic targets; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI179570

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.