Pub Date : 2025-11-20DOI: 10.1016/j.drudis.2025.104554
Xin-yuan Xu , Shu-ning Guo , Jing Li
Rheumatoid arthritis (RA) is a chronic inflammatory disease that is challenging to manage with current therapies. Toll-like receptors (TLRs) play a significant role in the pathogenesis of RA, making TLR-targeted therapies promising. This review summarizes recent advances in the characteristics of TLRs and highlights therapeutic strategies targeting TLRs. Representative agents such as OPN-305, OPN-301, imiquimod, and antidepressants have demonstrated therapeutic potential by modulating TLR signaling in RA pathological manifestations. TollB-001, a novel small molecular drug, represents a potential breakthrough in RA therapy. Despite promising preclinical and clinical outcomes with agents including IMO-3100, DV-1179, and R848, challenges remain regarding efficacy variability and immune-related safety. This review aims to provide insights into TLR-based interventions and inform the development of future strategies for more effective management.
{"title":"Advances and challenges in Toll-like receptor-targeted therapy for rheumatoid arthritis","authors":"Xin-yuan Xu , Shu-ning Guo , Jing Li","doi":"10.1016/j.drudis.2025.104554","DOIUrl":"10.1016/j.drudis.2025.104554","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease that is challenging to manage with current therapies. Toll-like receptors (TLRs) play a significant role in the pathogenesis of RA, making TLR-targeted therapies promising. This review summarizes recent advances in the characteristics of TLRs and highlights therapeutic strategies targeting TLRs. Representative agents such as OPN-305, OPN-301, imiquimod, and antidepressants have demonstrated therapeutic potential by modulating TLR signaling in RA pathological manifestations. TollB-001, a novel small molecular drug, represents a potential breakthrough in RA therapy. Despite promising preclinical and clinical outcomes with agents including IMO-3100, DV-1179, and R848, challenges remain regarding efficacy variability and immune-related safety. This review aims to provide insights into TLR-based interventions and inform the development of future strategies for more effective management.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104554"},"PeriodicalIF":7.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1016/j.drudis.2025.104551
Sharon E. Phares, Colin M. Young, Katie I. Phillip, Mark R. Trusheim
In the 8 years since the US Food and Drug Administration (FDA) approved the first durable cell and gene therapy (dCGT), there have been over 32 product-indication approvals, with many more products and indications in the pipeline. Using a novel multi-modal Markov chain Monte Carlo (MCMC)-based model, we estimate that, by 2034, the pipeline will yield ∼79 new product-indication approvals, an annual average of 29% year-over-year growth in treated patients, and US$28.8 billion in list price drug revenues, before any healthcare cost offsets, caregiving impacts, long-term social benefits, or other benefits from treating these additional patients.
{"title":"The next decade in cell and gene therapy","authors":"Sharon E. Phares, Colin M. Young, Katie I. Phillip, Mark R. Trusheim","doi":"10.1016/j.drudis.2025.104551","DOIUrl":"10.1016/j.drudis.2025.104551","url":null,"abstract":"<div><div>In the 8 years since the US Food and Drug Administration (FDA) approved the first durable cell and gene therapy (dCGT), there have been over 32 product-indication approvals, with many more products and indications in the pipeline. Using a novel multi-modal Markov chain Monte Carlo (MCMC)-based model, we estimate that, by 2034, the pipeline will yield ∼79 new product-indication approvals, an annual average of 29% year-over-year growth in treated patients, and US$28.8 billion in list price drug revenues, before any healthcare cost offsets, caregiving impacts, long-term social benefits, or other benefits from treating these additional patients.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104551"},"PeriodicalIF":7.5,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.drudis.2025.104535
Júlia Morales Rodrigues, Ana Paula Ferreira Leal, Danieli Fernanda Buccini, Octavio Luiz Franco
Inflammatory bowel diseases (IBDs) are chronic disorders affecting the gastrointestinal tract, causing severe inflammation and tissue damage. Current treatments often have adverse effects, underscoring the need for alternatives. This article is a short review of host defense peptides (HDPs), which have emerged as promising candidates for IBDs because of their antimicrobial and immunomodulatory properties. The HDPs cited include cathelicidins [e.g. LL-37-Tα1, lipid transfer protein (LTP), C-L, KR-12], defensins [e.g. human alpha defensin 5 (HD-5), human beta-defensin 2 (hBD2)], cecropins (e.g. CC34), microcins [e.g. microcin J25 (MccJ25)], brevinins (e.g. chensinin-1), proline-rich antimicrobial peptides (PrAMPs) (e.g. abaecin), type V peptides [e.g. vasopressin-neurophysin (VP-NP)], and alpha-melanocyte-stimulating hormone (α-MSH) (e.g. KPV). HDPs have immunoregulatory mechanisms, downregulating the nuclear factor kappa B (NF-κB) pathway, modulating cytokine release, and restoring homeostasis. The data suggest that HDPs have therapeutic potential for IBDs, offering a way to reduce side effects, and we focus on this issue here.
{"title":"Host defense peptides as a new drug lead to a strategy for inflammatory bowel disease.","authors":"Júlia Morales Rodrigues, Ana Paula Ferreira Leal, Danieli Fernanda Buccini, Octavio Luiz Franco","doi":"10.1016/j.drudis.2025.104535","DOIUrl":"10.1016/j.drudis.2025.104535","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBDs) are chronic disorders affecting the gastrointestinal tract, causing severe inflammation and tissue damage. Current treatments often have adverse effects, underscoring the need for alternatives. This article is a short review of host defense peptides (HDPs), which have emerged as promising candidates for IBDs because of their antimicrobial and immunomodulatory properties. The HDPs cited include cathelicidins [e.g. LL-37-Tα1, lipid transfer protein (LTP), C-L, KR-12], defensins [e.g. human alpha defensin 5 (HD-5), human beta-defensin 2 (hBD2)], cecropins (e.g. CC34), microcins [e.g. microcin J25 (MccJ25)], brevinins (e.g. chensinin-1), proline-rich antimicrobial peptides (PrAMPs) (e.g. abaecin), type V peptides [e.g. vasopressin-neurophysin (VP-NP)], and alpha-melanocyte-stimulating hormone (α-MSH) (e.g. KPV). HDPs have immunoregulatory mechanisms, downregulating the nuclear factor kappa B (NF-κB) pathway, modulating cytokine release, and restoring homeostasis. The data suggest that HDPs have therapeutic potential for IBDs, offering a way to reduce side effects, and we focus on this issue here.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104535"},"PeriodicalIF":7.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prostate cancer (PC), a significant global health burden, is further complicated by therapeutic resistance, systemic toxicity, and adverse effects on male fertility associated with conventional treatments. Small interfering RNA (siRNA)-based therapeutics offer molecular precision in oncogene silencing and tumor-promoting pathways. However, their clinical translation is constrained by challenges related to stability, delivery, and cellular uptake. Nanocarriers, including lipid-based, exosome-based, and other polymeric-based systems, could enhance stability, specificity, and efficacy. In this review, we highlight biomarker-targeted siRNA codelivery for PC, considering reproductive health and translational barriers, highlighting the future of fertility-preserving and quality of life-oriented therapies.
{"title":"siRNA-based Nanocarriers for Targeted Therapy in Prostate Cancer: Implications for Male Fertility Preservation","authors":"Krishna Kant Jangde , Rajeev Sharma , Dinesh Kumar Mishra , Pradyumna Kumar Mishra","doi":"10.1016/j.drudis.2025.104543","DOIUrl":"10.1016/j.drudis.2025.104543","url":null,"abstract":"<div><div>Prostate cancer (PC), a significant global health burden, is further complicated by therapeutic resistance, systemic toxicity, and adverse effects on male fertility associated with conventional treatments. Small interfering RNA (siRNA)-based therapeutics offer molecular precision in oncogene silencing and tumor-promoting pathways. However, their clinical translation is constrained by challenges related to stability, delivery, and cellular uptake. Nanocarriers, including lipid-based, exosome-based, and other polymeric-based systems, could enhance stability, specificity, and efficacy. In this review, we highlight biomarker-targeted siRNA codelivery for PC, considering reproductive health and translational barriers, highlighting the future of fertility-preserving and quality of life-oriented therapies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104543"},"PeriodicalIF":7.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.drudis.2025.104533
Thulile van Wyk, Clinton Rambanapasi, Ruan Gerber, Rose Hayeshi
Enhancing Africa’s readiness in terms of preclinical drug development is crucial for addressing healthcare needs and advancing pharmaceutical innovation on the continent. The process of bringing new medicines to market in Africa hinges on its ability to navigate the complexities of preclinical drug development effectively. Although various issues limit progression, good laboratory practice (GLP)-compliant preclinical trials constitute a significant factor. Here, we examine Africa’s ability to bring its medicines to market, with a specific focus on principles and practices of GLP in preclinical drug development. While significant strides have been made in human resources and the establishment of GLP-certified facilities for preclinical research, further effort is required. Addressing such GLP-related challenges would unlock opportunities for pharmaceutical market expansion in Africa.
{"title":"Is Africa ready to bring to market its own medicines? A focus on GLP preclinical drug development","authors":"Thulile van Wyk, Clinton Rambanapasi, Ruan Gerber, Rose Hayeshi","doi":"10.1016/j.drudis.2025.104533","DOIUrl":"10.1016/j.drudis.2025.104533","url":null,"abstract":"<div><div>Enhancing Africa’s readiness in terms of preclinical drug development is crucial for addressing healthcare needs and advancing pharmaceutical innovation on the continent. The process of bringing new medicines to market in Africa hinges on its ability to navigate the complexities of preclinical drug development effectively. Although various issues limit progression, good laboratory practice (GLP)-compliant preclinical trials constitute a significant factor. Here, we examine Africa’s ability to bring its medicines to market, with a specific focus on principles and practices of GLP in preclinical drug development. While significant strides have been made in human resources and the establishment of GLP-certified facilities for preclinical research, further effort is required. Addressing such GLP-related challenges would unlock opportunities for pharmaceutical market expansion in Africa.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104533"},"PeriodicalIF":7.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.drudis.2025.104530
Jamal Tazi (Professor Emeritus, University of Montpellier; CNRS – IGMM; Co-founder of Splicos and Abivax)
{"title":"From HIV to Inflammation: How RNA Biology Redefined Drug Discovery","authors":"Jamal Tazi (Professor Emeritus, University of Montpellier; CNRS – IGMM; Co-founder of Splicos and Abivax)","doi":"10.1016/j.drudis.2025.104530","DOIUrl":"10.1016/j.drudis.2025.104530","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104530"},"PeriodicalIF":7.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.drudis.2025.104534
Bhargav Ranapangu , Monika Sandhu , Atish T. Paul
Natural products (NPs) have historically served as sources of bioactive molecules with considerable clinical therapeutic potential. Their complex molecular mechanisms can be investigated through in vitro proteomics utilizing liquid chromatography (LC)-mass spectrometry (MS) and related techniques. In this review, we provide a framework for exploring protein-level alterations caused by NPs using both top-down and bottom-up proteomic methods. We comprehensively explore the importance of various components, including instrument selection, cell/tissue treatment, protein extraction, digestion, and strategies, and also highlight the significance of both label-free and label-based quantification, bioinformatics techniques, and data standardization processes. In addition, we discuss several case studies in which LC-MS-based proteomics has been used to provide a thorough understanding of cellular pathways affected by NPs, providing crucial insights for drug discovery and therapeutic strategies.
{"title":"LC-MS-based proteomics: insights into natural product-directed cellular targeting","authors":"Bhargav Ranapangu , Monika Sandhu , Atish T. Paul","doi":"10.1016/j.drudis.2025.104534","DOIUrl":"10.1016/j.drudis.2025.104534","url":null,"abstract":"<div><div>Natural products (NPs) have historically served as sources of bioactive molecules with considerable clinical therapeutic potential. Their complex molecular mechanisms can be investigated through <em>in vitro</em> proteomics utilizing liquid chromatography (LC)-mass spectrometry (MS) and related techniques. In this review, we provide a framework for exploring protein-level alterations caused by NPs using both top-down and bottom-up proteomic methods. We comprehensively explore the importance of various components, including instrument selection, cell/tissue treatment, protein extraction, digestion, and strategies, and also highlight the significance of both label-free and label-based quantification, bioinformatics techniques, and data standardization processes. In addition, we discuss several case studies in which LC-MS-based proteomics has been used to provide a thorough understanding of cellular pathways affected by NPs, providing crucial insights for drug discovery and therapeutic strategies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104534"},"PeriodicalIF":7.5,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.drudis.2025.104532
Peixiang Ma , Hailong Ma , Jie Li , Wanting Bi , Shuning Zhang , Wei Hou , Hongtao Xu
Lipid nanoparticle (LNP)-based gene therapy holds great promise to revolutionize modern medicine. To address the challenges associated with LNP-based mRNA delivery, we systematically examine combinatorial chemistry approaches that facilitate the rapid synthesis of ionizable lipid libraries for high-throughput LNP screening, the application of click and bioorthogonal chemistry for the surface modification of LNPs with targeting ligands, and recent advances in barcoding technologies enabling comprehensive in vitro and in vivo evaluation of LNP performance. Furthermore, we outline the key design considerations and crucial challenges associated with developing LNPs for effective mRNA delivery, and propose strategic approaches to expand lipid libraries and enhance high-throughput screening (HTS) capabilities.
{"title":"Combinatorial chemistry and click chemistry for the optimization of lipid nanoparticles to enhance RNA delivery","authors":"Peixiang Ma , Hailong Ma , Jie Li , Wanting Bi , Shuning Zhang , Wei Hou , Hongtao Xu","doi":"10.1016/j.drudis.2025.104532","DOIUrl":"10.1016/j.drudis.2025.104532","url":null,"abstract":"<div><div>Lipid nanoparticle (LNP)-based gene therapy holds great promise to revolutionize modern medicine. To address the challenges associated with LNP-based mRNA delivery, we systematically examine combinatorial chemistry approaches that facilitate the rapid synthesis of ionizable lipid libraries for high-throughput LNP screening, the application of click and bioorthogonal chemistry for the surface modification of LNPs with targeting ligands, and recent advances in barcoding technologies enabling comprehensive <em>in vitro</em> and <em>in vivo</em> evaluation of LNP performance. Furthermore, we outline the key design considerations and crucial challenges associated with developing LNPs for effective mRNA delivery, and propose strategic approaches to expand lipid libraries and enhance high-throughput screening (HTS) capabilities.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104532"},"PeriodicalIF":7.5,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.drudis.2025.104529
Anne R. Pariser , Violeta Stoyanova-Beninska , Oxana Iliach , Reda Jundi , Kerry Jo Lee , Hanako Morikawa , Samantha Parker , Caroline Pothet , Marco Rizzi , Julienne Vaillancourt , Ana Hidalgo-Simon
Large time gaps are frequently observed between approvals of orphan products by different jurisdictions. A retrospective review of publicly accessible information for new orphan medicines approvals between 2021 and 2022 was performed to quantify the types of evidence required and timeframes for initial and subsequent approvals in six different regions. We identified 53 orphan products: 91% were approved in two or more regions, and 69% relied upon the same/highly similar types of evidence for marketing authorization. Time between subsequent marketing authorizations varied widely, with a mean of 1 year for the second, increasing to 3 years for the third through sixth authorizations. A high degree of consistency in the evidence accepted across different regions was found, and global collaborative programs might help accelerate timelines.
{"title":"Non-oncologic orphan drug approvals across the world: Types of evidence required and time to approval","authors":"Anne R. Pariser , Violeta Stoyanova-Beninska , Oxana Iliach , Reda Jundi , Kerry Jo Lee , Hanako Morikawa , Samantha Parker , Caroline Pothet , Marco Rizzi , Julienne Vaillancourt , Ana Hidalgo-Simon","doi":"10.1016/j.drudis.2025.104529","DOIUrl":"10.1016/j.drudis.2025.104529","url":null,"abstract":"<div><div>Large time gaps are frequently observed between approvals of orphan products by different jurisdictions. A retrospective review of publicly accessible information for new orphan medicines approvals between 2021 and 2022 was performed to quantify the types of evidence required and timeframes for initial and subsequent approvals in six different regions. We identified 53 orphan products: 91% were approved in two or more regions, and 69% relied upon the same/highly similar types of evidence for marketing authorization. Time between subsequent marketing authorizations varied widely, with a mean of 1 year for the second, increasing to 3 years for the third through sixth authorizations. A high degree of consistency in the evidence accepted across different regions was found, and global collaborative programs might help accelerate timelines.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104529"},"PeriodicalIF":7.5,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.drudis.2025.104528
Satveer Jagwani , Laura Musumeci , Lizbeth Flores , Gerardo G. Mackenzie , Mansoor M. Amiji
Pancreatic cancer (PC) remains one of the most lethal malignancies, characterized by aggressive progression, late detection, and limited response to current therapies. Recent research has revealed that the gastrointestinal and intratumoral microbiomes are key modulators of immune regulation, metabolism, and epigenetic pathways, influencing tumor progression and therapeutic efficacy. This review summarizes the complex microbiome–PC interplay, emphasizing microbial modulation of inflammation, immunity, and treatment resistance. We also highlight microbiome-targeted strategies, such as probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, along with advanced drug-delivery platforms – including nanoparticles, engineered bacteria, and stimuli-responsive systems – for precise microbiome modulation. Integrating microbiome science with immunotherapy, nanotechnology, and epigenetic reprogramming offers promising opportunities to improve outcomes in PC.
{"title":"Strategic modulation of the gastrointestinal microbiome to enhance pancreatic cancer immunotherapy","authors":"Satveer Jagwani , Laura Musumeci , Lizbeth Flores , Gerardo G. Mackenzie , Mansoor M. Amiji","doi":"10.1016/j.drudis.2025.104528","DOIUrl":"10.1016/j.drudis.2025.104528","url":null,"abstract":"<div><div>Pancreatic cancer (PC) remains one of the most lethal malignancies, characterized by aggressive progression, late detection, and limited response to current therapies. Recent research has revealed that the gastrointestinal and intratumoral microbiomes are key modulators of immune regulation, metabolism, and epigenetic pathways, influencing tumor progression and therapeutic efficacy. This review summarizes the complex microbiome–PC interplay, emphasizing microbial modulation of inflammation, immunity, and treatment resistance. We also highlight microbiome-targeted strategies, such as probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, along with advanced drug-delivery platforms – including nanoparticles, engineered bacteria, and stimuli-responsive systems – for precise microbiome modulation. Integrating microbiome science with immunotherapy, nanotechnology, and epigenetic reprogramming offers promising opportunities to improve outcomes in PC.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 12","pages":"Article 104528"},"PeriodicalIF":7.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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