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This review summarizes resistance mechanisms and nanoparticle-based strategies delivering TRAIL peptides, TRAIL-R agonists, and TRAIL genes, and also discusses combination regimens with chemotherapy.",{"@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/nano-trail-a-promising-path-to-cancer-therapy/377745/",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/nano-trail-a-promising-path-to-cancer-therapy/377745.png","ImageObject",300,407,{"name":42,"@type":43},"Ivy","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-24","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does TRAIL/Apo-2L play in cancer-cell apoptosis?","Question",{"text":63,"@type":64},"TRAIL/Apo-2L triggers apoptosis by binding to death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). 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Cancer Drug Resist 2023;6:78-102 DOI: 10.20517/cdr.2022.82  \nCancer Drug Resistance  \nReview Open Access  \nNano-TRAIL: a promising path to cancer therapy  \nSiri Chandana Gampa1, Sireesha V. Garimella1, SanthiLatha Pandrangi2  \n1 Department of Biotechnology, Institute of Science, GITAM (Deemed to be University), Andhra Pradesh 530045, India. 2 Department of Biochemistry and Bioinformatics, Institute of Science, GITAM (Deemed to be University), Andhra Pradesh 530045, India.  \nCorrespondence to: Dr Sireesha V. Garimella, Department of Biotechnology, Institute of Science, GITAM (Deemed to be  \nUniversity), Gandhi Nagar, Rushikonda, Andhra Pradesh 530045, India. E-mail: [sgarimel@gitam.edu](sgarimel@gitam.edu)  \n[How to cite this article:](How to cite this article: Gampa SC)[ Gampa SC](How to cite this article: Gampa SC), Garimella SV, Pandrangi S. Nano-TRAIL: a promising path to cancer therapy. Cancer Drug Resist 2023;6:79-103 . [https://dx.doi.org/10.20517/cdr.2022.82](https://dx.doi.org/10.20517/cdr.2022.82)  \nReceived: 30 Jun 2022 First Decision: 20 Sep 2022 Revised: 20 Oct 2022 Accepted: 4 Jan 2023 Published: 1 Feb 2023 Academic Editors: Xiang-Yang Shi, Godefridus J. Peters Copy Editor: Ke-Cui Yang Production Editor: Ke-Cui Yang  \nAbstract  \nTumor Necrosis Factor-Related Apoptosis-Inducing Ligand, also called apo-2 ligand (TRAIL/Apo-2L), is a cytokine that triggers apoptosis by binding to TRAIL-R1 (DR4) and TRAIL-R2 (DR5) death receptors. Apoptosis occurs through either the extrinsic or intrinsic pathway. The administration of recombinant human TRAIL (rhTRAIL) or TRAIL-receptor (TRAIL-R) agonists promotes apoptosis preferentially in cancerous cells over normal cells in vitro; this phenomenon has also been observed in clinical studies. The limited efficacy of rhTRAIL in clinical trials could be attributed to drug resistance, short half-life, targeted delivery issues, and off-target toxicities. Nanoparticles are excellent drug and gene delivery systems characterized by improved permeability and retention, increased stability and biocompatibility, and precision targeting. In this review, we discuss resistance mechanisms to TRAIL and methods to overcome TRAIL resistance by using nanoparticle-based formulations developed for the delivery of TRAIL peptides, TRAIL-R agonists, and TRAIL genes to cancer cells. We also discuss combinatorial approaches of chemotherapeutic drugs with TRAIL. These studies demonstrate TRAIL’s potential as an anticancer agent.  \nKeywords: TRAIL, cancer cells, nanoparticles, apoptosis, nanomedicine  \nINTRODUCTION  \nCancer is the aberrant growth of cells capable of invading and metastasizing to other body parts. It is one of the leading causes of death, with approximately 10 million deaths expected globally by 2020, according to  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License ([https://creativecommons.org/l](https://creativecommons.org/l)icenses/by/4 .0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.  \n[www.cdrjournal.com](www.cdrjournal.com)  \nPage 79 Gampa et al. Cancer Drug Resist 2023;6:78-102  [https://dx.doi.org/10.20517/cdr.2022.82](https://dx.doi.org/10.20517/cdr.2022.82)  \n[the World Health Organization. There are various treatment options](the World Health Organization. There are various treatment options), including surgery, chemotherapy, targeted therapy, radiation therapy, immunotherapy, and hormone therapy[1] . One branch of chemo/radiotherapy is targeted therapy that targets the tumor alone (for example, tumor vasculature or intracellular organelles, leaving the surrounding cells unaffected) . This approach results in precise treatment of the tumor a","cbCaifk27MOYbt4t","https://ap.wps.com/l/cbCaifk27MOYbt4t","pdf",3102591,25,"English","# Abstract\n# Introduction\n## Cancer and targeted therapy overview\n## TRAIL and its receptor system\n# TRAIL and TRAIL receptors","[{\"question\":\"What role does TRAIL/Apo-2L play in cancer-cell apoptosis?\",\"answer\":\"TRAIL/Apo-2L triggers apoptosis by binding to death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Apoptosis proceeds through extrinsic or intrinsic pathways.\"},{\"question\":\"Why has rhTRAIL shown limited efficacy in clinical trials?\",\"answer\":\"The review attributes limited efficacy to drug resistance, short half-life, targeted delivery challenges, and off-target toxicities.\"},{\"question\":\"How do nanoparticle-based formulations help overcome TRAIL resistance?\",\"answer\":\"The review describes nanoparticle-based delivery of TRAIL peptides, TRAIL-R agonists, and TRAIL genes to cancer cells, aiming for improved stability and more precise targeting while countering resistance mechanisms.\"}]","Nano-TRAIL - a promising path to cancer therapy | PDF",1790226984,63]