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Targeting apoptotic pathways for cancer therapy
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, inc...
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| Published in: | The Journal of clinical investigation 2024-07, Vol.134 (14), p.1-12 |
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| container_end_page | 12 |
| container_issue | 14 |
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| container_title | The Journal of clinical investigation |
| container_volume | 134 |
| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1172/JCI179570 |
| format | article |
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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.</description><identifier>ISSN: 1558-8238</identifier><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI179570</identifier><identifier>PMID: 39007268</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>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</subject><ispartof>The Journal of clinical investigation, 2024-07, Vol.134 (14), p.1-12</ispartof><rights>COPYRIGHT 2024 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jul 2024</rights><rights>2024 Tian et al. 2024 Tian et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c463t-58891efa6b6d4676a416430a2f3744b7f9abe18cee8540ab0f77a9b37df2776d3</cites><orcidid>0000-0003-1276-8466 ; 0000-0002-9577-8266</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245162/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245162/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39007268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Xiaobing</creatorcontrib><creatorcontrib>Srinivasan, Praveen R</creatorcontrib><creatorcontrib>Tajiknia, Vida</creatorcontrib><creatorcontrib>Sanchez Sevilla Uruchurtu, Ashley F</creatorcontrib><creatorcontrib>Seyhan, Attila A</creatorcontrib><creatorcontrib>Carneiro, Benedito A</creatorcontrib><creatorcontrib>De La Cruz, Arielle</creatorcontrib><creatorcontrib>Pinho-Schwermann, Maximilian</creatorcontrib><creatorcontrib>George, Andrew</creatorcontrib><creatorcontrib>Zhao, Shuai</creatorcontrib><creatorcontrib>Strandberg, Jillian</creatorcontrib><creatorcontrib>Di Cristofano, Francesca</creatorcontrib><creatorcontrib>Zhang, Shengliang</creatorcontrib><creatorcontrib>Zhou, Lanlan</creatorcontrib><creatorcontrib>Raufi, Alexander G</creatorcontrib><creatorcontrib>Navaraj, Arunasalam</creatorcontrib><creatorcontrib>Zhang, Yiqun</creatorcontrib><creatorcontrib>Verovkina, Nataliia</creatorcontrib><creatorcontrib>Ghandali, Maryam</creatorcontrib><creatorcontrib>Ryspayeva, Dinara</creatorcontrib><creatorcontrib>El-Deiry, Wafik S</creatorcontrib><title>Targeting apoptotic pathways for cancer therapy</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>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.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic drugs</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bcl-2 protein</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell death</subject><subject>Cellular stress response</subject><subject>Chemotherapy</subject><subject>Competition</subject><subject>Cytochrome</subject><subject>Development and progression</subject><subject>Drug delivery</subject><subject>Drug development</subject><subject>FDA approval</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Lymphoma</subject><subject>Molecular targeted therapy</subject><subject>Mutation</subject><subject>Neoplasms - 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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. 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| source | Open Access: PubMed Central; EZB Electronic Journals Library |
| 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 |
| title | Targeting apoptotic pathways for cancer therapy |
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