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This review synthesizes apoptotic and autophagy-dependent pathways and additionally covers other RCD mechanisms to clarify their roles in therapy resistance. It integrates current mechanistic insights to support novel strategies against drug-resistant cancer.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/challenges-of-regulated-cell-death-implications-for-therapy-resistance-in-cancer/337930/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/challenges-of-regulated-cell-death-implications-for-therapy-resistance-in-cancer/337930.png","ImageObject",300,407,{"name":42,"@type":43},"Aria","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is regulated cell death and why is it important in cancer?","Question",{"text":63,"@type":64},"Regulated cell death (RCD) is a controlled process of cell demise that supports organismal homeostasis. In cancer, alterations in RCD modes can affect tumor progression and contribute to therapy resistance.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which RCD types are highlighted as major categories in the review?",{"text":68,"@type":64},"The review lists apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, parthanatos, entosis, cuproptosis, disulfidptosis, lysosome-dependent cell death, alkaliptosis, and immunogenic cell death.",{"name":70,"@type":61,"acceptedAnswer":71},"How does RCD relate to therapy resistance and treatment failure?",{"text":72,"@type":64},"Cancer cells can evade specific cell death mechanisms, undermining the execution of lethal pathways such as apoptotic cascades. These pathway alterations are described as a common reason for drug resistance and therapy failure.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},337930,1790226631,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","cells  \nReview  \nChallenges of Regulated Cell Death: Implications for Therapy Resistance in Cancer  \nMaria D’Amico 1 and Francesca De Amicis 1,2, *  \nCitation: D’Amico, M.; De Amicis, F. Challenges of Regulated Cell Death: Implications for Therapy Resistance in Cancer. Cells 2024, 13, 1083. [https://](https://)[ ](https://)[doi.org/10.3390/cells13131083](doi.org/10.3390/cells13131083)  \nAcademic Editor: Mustapha Kandouz  \nReceived: 22 April 2024  \nRevised: 18 June 2024  \nAccepted: 20 June 2024  \nPublished: 22 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy  \n2 Health Center, University of Calabria, 87036 Rende, Italy  \n* Correspondence: [francesca.deamicis@unical.it](francesca.deamicis@unical.it)  \nAbstract: Regulated cell death, a regulatory form of cell demise, has been extensively studied in multicellular organisms. It plays a pivotal role in maintaining organismal homeostasis under normal and pathological conditions. Although alterations in various regulated cell death modes are hallmark features of tumorigenesis, they can have divergent effects on cancer cells. Consequently, there is a growing interest in targeting these mechanisms using small-molecule compounds for therapeutic purposes, with substantial progress observed across various human cancers. This review focuses on summarizing key signaling pathways associated with apoptotic and autophagy-dependent cell death. Additionally, it explores crucial pathways related to other regulated cell death modes in the context of cancer. The discussion delves into the current understanding of these processes and their implications in cancer treatment, aiming to illuminate novel strategies to combat therapy resistance and enhance overall cancer therapy.  \nKeywords: apoptosis; autophagy; ferroptosis; pyroptosis; immunogenic; drug resistance  \n1. Introduction  \nOver the past few decades, extensive experimental evidence provided detailed insights into genetically encoded mechanisms that target and eliminate unnecessary, irreversibly damaged or potentially harmful cells. When mammalian cells encounter irreversible disruptions in their internal or external microenvironment, they may trigger various signal transduction pathways, ultimately resulting in cell death. These regulated cell death (RCD) processes are driven and propagated by complex molecular mechanisms that are highly interconnected. Furthermore, each type of RCD can display a wide range of morphological traits and immunomodulatory properties, spanning from anti-inflammatory and toleranceinducing effects to promoting inflammation and immunogenic responses [1] .  \nCurrently known RCDs mainly include the following: apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, parthanatos, entosis, cuproptosis, disulfidptosis, lysosomedependent cell death, alkaliptosis, and immunogenic cell death. These processes have been extensively studied in multicellular organisms, where they play crucial roles in maintaining organismal homeostasis in both normal and disease conditions [2] .  \nParticularly, RCD operates as a natural barrier that protects against cancer development through dedicated molecular machinery. The mechanisms can be targeted through pharmacological or genetic interventions; however, alteration of specific cell death pathways in cancer is often responsible for drug resistance, resulting in therapy failure [3] .  \nThe evasion of different cell death mechanisms is considered an indisputable hallmark of cancer [4,5] . For example, cancer cells frequently exhibit overexpression of numerous proteins that a","cbCaik1qBK2EhiMx","https://ap.wps.com/l/cbCaik1qBK2EhiMx","pdf",1058077,25,"English","# Abstract\n# Keywords\n# Introduction\n## Regulated cell death as molecularly driven homeostasis\n## Major categories of RCD and cancer relevance\n## RCD evasion as a hallmark of cancer and therapy failure\n# Mechanistic links to drug resistance in cancer","[{\"question\":\"What is regulated cell death and why is it important in cancer?\",\"answer\":\"Regulated cell death (RCD) is a controlled process of cell demise that supports organismal homeostasis. In cancer, alterations in RCD modes can affect tumor progression and contribute to therapy resistance.\"},{\"question\":\"Which RCD types are highlighted as major categories in the review?\",\"answer\":\"The review lists apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, parthanatos, entosis, cuproptosis, disulfidptosis, lysosome-dependent cell death, alkaliptosis, and immunogenic cell death.\"},{\"question\":\"How does RCD relate to therapy resistance and treatment failure?\",\"answer\":\"Cancer cells can evade specific cell death mechanisms, undermining the execution of lethal pathways such as apoptotic cascades. These pathway alterations are described as a common reason for drug resistance and therapy failure.\"}]","Challenges of Regulated Cell Death - Implications for Therapy Resistance in Cancer | PDF",1790021218,63]