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Drug resistance in cancer radiotherapy: From mechanisms to overcoming strategies. 肿瘤放疗中的耐药：从机制到克服策略。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI: 10.1016/j.phrs.2026.108380
Yang Chen, Chao-Yun Cai, Xiao-Chen Xu, Zheng Yang, Jia Li, Qingming Pan, Lei Wang, Wei Luo, Zhe-Sheng Chen, Leli Zeng, Yihang Pan
{"title":"Drug resistance in cancer radiotherapy: From mechanisms to overcoming strategies.","authors":"Yang Chen, Chao-Yun Cai, Xiao-Chen Xu, Zheng Yang, Jia Li, Qingming Pan, Lei Wang, Wei Luo, Zhe-Sheng Chen, Leli Zeng, Yihang Pan","doi":"10.1016/j.phrs.2026.108380","DOIUrl":"10.1016/j.phrs.2026.108380","url":null,"abstract":"<p><p>Radiotherapy is frequently combined with chemotherapy, targeted therapy and immunotherapy to improve the efficacy of cancer treatment. Nevertheless, some radioresistant cancer cells seem to possess higher drug resistance, leading to failure of cancer treatment. Thus, it is crucial to explore the mechanisms of drug resistance in cancer RT. This review outlines molecular, cellular, and microenvironmental adaptations in cancer RT. These adaptations confer enhanced chemotherapy resistance in cancer cells surviving from ionizing radiation (IR). In addition, RT also activates oncogene signaling pathways, induces epigenetic remodeling and alters post-translational modifications, collectively driving resistance to targeted therapy. RT alters tumor intrinsic properties, promotes immunosuppressive effects and remodels TME, thus inducing immunotherapy resistance. Various emerging strategies including phytochemicals, small molecules, synthetic compounds, macromolecules, nanoparticles, photodynamic therapy (PDT), photothermal therapy (PTT), MicroRNA (miRNA) therapy, PROTACs, adoptive cell therapies, and engineered Salmonella, have been developed to overcome radioresistance and drug resistance in cancer RT. We highlight the importance of evaluating therapeutic effects and side effects of these emerging strategies. Through summarizing mechanisms and emerging strategies for drug resistance in cancer RT, this review aims to clarify obstacles in combined cancer treatment and guide future direction of research on cancer therapy.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"108380"},"PeriodicalIF":12.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713460","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}
引用次数: 0
From indirect regulation to multi-layered metabolic control in MASLD: Multi-receptor agonism and microbiota-metabolite functional convergence. MASLD从间接调控到多层代谢控制：多受体激动作用和微生物群代谢物功能趋同。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-09-01 Epub Date: 2026-08-08 DOI: 10.1016/j.phrs.2026.108369
Sini Zhou, Ling Dong
{"title":"From indirect regulation to multi-layered metabolic control in MASLD: Multi-receptor agonism and microbiota-metabolite functional convergence.","authors":"Sini Zhou, Ling Dong","doi":"10.1016/j.phrs.2026.108369","DOIUrl":"10.1016/j.phrs.2026.108369","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown clinical efficacy in metabolic dysfunction-associated steatotic liver disease (MASLD), yet their therapeutic performance appears limited in several recurring settings, including advanced fibrosis, metabolically milder populations, and treatment discontinuation. These limitations suggest that treatment responses are shaped not only by pharmacological potency, but also by the regulatory systems through which GLP-1RAs act. Here, we propose a conceptual multi-layered framework in which GLP-1R-based therapies improve hepatic outcomes predominantly, although not exclusively, through indirect and systemic metabolic regulation. Within this framework, therapeutic responses may be influenced by the integrity of intrahepatic and systemic signaling networks, the magnitude of baseline metabolic perturbation, and the persistence of pharmacological input, which can be interpreted as structural, contextual, and temporal constraints. Multi-receptor agonists may partially mitigate these constraints by expanding regulatory inputs through glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon receptor (GCGR) co-activation. However, receptor-level modulation alone may remain insufficient to ensure durable responses after treatment withdrawal. We further discuss the gut microbiota and its metabolites as a candidate system-level regulatory layer that integrates host metabolic, immune, and endocrine signaling. Across diverse interventions, convergence appears more consistent at the level of microbiota-associated metabolic functions than taxonomic composition, but its causal significance remains incompletely established. Cross-intervention convergence analysis may therefore serve as a hypothesis-generating strategy to identify recurrent microbiota-metabolite axes with potential mechanistic and therapeutic relevance.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"108369"},"PeriodicalIF":12.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697609","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}
引用次数: 0
Multifaceted role of DEPP1: Linking oxidative stress with autophagy, and beyond. DEPP1的多方面作用：将氧化应激与自噬联系起来，以及其他。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI: 10.1016/j.phrs.2026.108381
Chuxin Zhang, Jiahao Wu, Jinhua Han, Sicheng Feng, Jiahui Gao, Fafeng Cheng, Qingguo Wang, Changxiang Li, Xueqian Wang
{"title":"Multifaceted role of DEPP1: Linking oxidative stress with autophagy, and beyond.","authors":"Chuxin Zhang, Jiahao Wu, Jinhua Han, Sicheng Feng, Jiahui Gao, Fafeng Cheng, Qingguo Wang, Changxiang Li, Xueqian Wang","doi":"10.1016/j.phrs.2026.108381","DOIUrl":"10.1016/j.phrs.2026.108381","url":null,"abstract":"<p><p>Decidual protein induced by progesterone 1 (DEPP1), also known as DEPP or C10ORF10, was originally identified as a progesterone-induced protein in endometrial stromal cells. Over the past two decades, research has progressively elucidated its involvement in various biological processes such as energy metabolism, redox regulation, and cellular autophagy. Additionally, DEPP1 has been implicated in the pathogenesis of several diseases, including diabetes, atherosclerosis, ischemic cardiomyopathy, breast cancer, and colon cancer. In this review, we systematically summarise the research progress on DEPP1, with particular emphasis on its molecular mechanisms in the crosstalk between oxidative stress and autophagy. Its cellular localization and functional uniqueness are discussed within the context of the classical redox-autophagy regulatory network. Furthermore, key issues in DEPP1 research and its potential translational applications are discussed to provide insights and perspectives for future studies centred on DEPP1.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"108381"},"PeriodicalIF":12.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713372","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}
引用次数: 0
Corrigendum to “PET radiotracers targeting MDM2 protein interaction: From preclinical validation to first-in-human studies” [Pharmacol. Res. (2026) 230 108314] “靶向MDM2蛋白相互作用的PET放射性示踪剂：从临床前验证到首次人体研究”的勘误表[Pharmacol]。Res.(2026) 230 108314]。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-08-01 Epub Date: 2026-06-25 DOI: 10.1016/j.phrs.2026.108324
Chengxue He, Zhen Wang, Nina Zhou, Xiangxi Meng, Hua Zhu, Chunyi Hao, Zhi Yang, Lei Xia
{"title":"Corrigendum to “PET radiotracers targeting MDM2 protein interaction: From preclinical validation to first-in-human studies” [Pharmacol. Res. (2026) 230 108314]","authors":"Chengxue He,&nbsp;Zhen Wang,&nbsp;Nina Zhou,&nbsp;Xiangxi Meng,&nbsp;Hua Zhu,&nbsp;Chunyi Hao,&nbsp;Zhi Yang,&nbsp;Lei Xia","doi":"10.1016/j.phrs.2026.108324","DOIUrl":"10.1016/j.phrs.2026.108324","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"230 ","pages":"Article 108324"},"PeriodicalIF":12.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “BRD4 inhibitor suppresses melanoma metastasis via the SPINK6 EGFR-EphA2 pathway” [Pharmacol. Res. 187 (2023) 106609] “BRD4抑制剂通过SPINK6 EGFR-EphA2途径抑制黑色素瘤转移”的更正[Pharmacol]。Res. 187(2023) 106609]。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-08-01 Epub Date: 2026-07-14 DOI: 10.1016/j.phrs.2026.108338
Rui Hu, Yao Li, Ying Guo, Xin Li, Songtao Du, Mengting Liao, Huihui Hou, Hongyin Sun, Shuang Zhao, Juan Su, Xiang Chen, Mingzhu Yin
{"title":"Corrigendum to “BRD4 inhibitor suppresses melanoma metastasis via the SPINK6 EGFR-EphA2 pathway” [Pharmacol. Res. 187 (2023) 106609]","authors":"Rui Hu,&nbsp;Yao Li,&nbsp;Ying Guo,&nbsp;Xin Li,&nbsp;Songtao Du,&nbsp;Mengting Liao,&nbsp;Huihui Hou,&nbsp;Hongyin Sun,&nbsp;Shuang Zhao,&nbsp;Juan Su,&nbsp;Xiang Chen,&nbsp;Mingzhu Yin","doi":"10.1016/j.phrs.2026.108338","DOIUrl":"10.1016/j.phrs.2026.108338","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"230 ","pages":"Article 108338"},"PeriodicalIF":12.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: Current pharmacological challenges of Treatment-Resistant Depression 社论：目前难治性抑郁症的药理学挑战。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-08-01 Epub Date: 2026-07-06 DOI: 10.1016/j.phrs.2026.108336
Larissa Junkes, Antonio E. Nardi
{"title":"Editorial: Current pharmacological challenges of Treatment-Resistant Depression","authors":"Larissa Junkes,&nbsp;Antonio E. Nardi","doi":"10.1016/j.phrs.2026.108336","DOIUrl":"10.1016/j.phrs.2026.108336","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"230 ","pages":"Article 108336"},"PeriodicalIF":12.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic interactions of host-gut microbiota: Shaping the future of precision diagnosis and therapeutic discovery in gastrointestinal cancers 宿主-肠道微生物群的代谢相互作用：塑造胃肠道癌症精确诊断和治疗发现的未来。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-07-01 Epub Date: 2026-05-29 DOI: 10.1016/j.phrs.2026.108273
Jiaxin Zhang, Jingjing Liu, Yuan Tian, Wei Jia, Ge Zhang, Aiping Lyu, Haitao Lyu
{"title":"Metabolic interactions of host-gut microbiota: Shaping the future of precision diagnosis and therapeutic discovery in gastrointestinal cancers","authors":"Jiaxin Zhang,&nbsp;Jingjing Liu,&nbsp;Yuan Tian,&nbsp;Wei Jia,&nbsp;Ge Zhang,&nbsp;Aiping Lyu,&nbsp;Haitao Lyu","doi":"10.1016/j.phrs.2026.108273","DOIUrl":"10.1016/j.phrs.2026.108273","url":null,"abstract":"<div><div>This collection of reviews and research articles highlights the diagnostic and therapeutic potential of gut microbial metabolites across various gastrointestinal cancers, including but not limited to hepatobiliary and pancreatic cancers, gastric cancer, and cholangiocarcinoma. Numerous gut microbial metabolites have been observed to mechanistically regulate cancer cell proliferation and development, supporting their utility as molecular biomarkers for clinical diagnosis and as targets for precision interventions. However, most functional metabolites derived from both host cancer tissues and the gut microbiota remain structurally unidentified; their functional features are largely unexplored due to limitations in conventional measurement technologies. To address these challenges, we propose a transformative functional metabolomics approach—S<sup>2</sup>M<sup>2</sup>ART (Single-Cell Spatial Metabolomics Metagenomics-Artificial Intelligence Recombinational Toolkit)—which will leverage AI-powered multimodal omics and single-cell, spatially-resolved analyses to decode the molecular functions and mechanisms of these metabolites in gastrointestinal cancer development. Collectively, this innovative technique will substantially enhance the applicability and translational potential of microbial metabolites in gastrointestinal cancers and beyond.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"229 ","pages":"Article 108273"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Reconstitution of gut microbiota by medicinal plant isoflavones ameliorates heart failure with preserved ejection fraction” [Pharmacol. Res., Vol 228, June 2026, 108199] “药用植物异黄酮重建肠道微生物群改善保留射血分数的心力衰竭”的勘误表[药学]。文献，Vol . 228, June 2026, 108199]。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-07-01 Epub Date: 2026-06-03 DOI: 10.1016/j.phrs.2026.108277
Jinghan Lin, Qianhui Zhu, Tao Wang, Jingzu Sun, Ruopeng Yin, Yuting Zhang, Huanqin Dai, Shanshan Qiao, Shenghan Gao, Songnian Hu, Hongwei Liu
{"title":"Corrigendum to “Reconstitution of gut microbiota by medicinal plant isoflavones ameliorates heart failure with preserved ejection fraction” [Pharmacol. Res., Vol 228, June 2026, 108199]","authors":"Jinghan Lin,&nbsp;Qianhui Zhu,&nbsp;Tao Wang,&nbsp;Jingzu Sun,&nbsp;Ruopeng Yin,&nbsp;Yuting Zhang,&nbsp;Huanqin Dai,&nbsp;Shanshan Qiao,&nbsp;Shenghan Gao,&nbsp;Songnian Hu,&nbsp;Hongwei Liu","doi":"10.1016/j.phrs.2026.108277","DOIUrl":"10.1016/j.phrs.2026.108277","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"229 ","pages":"Article 108277"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Placebo design, reporting compliance, and methodological problems in randomized, placebo-controlled trials of Chinese herbal medicine: A cross-sectional study” [Pharmacol. Res. 229 (2026) 108244] 《中草药随机、安慰剂对照试验中的安慰剂设计、报告依从性和方法学问题：一项横断面研究》的勘误表[Pharmacol]。[Res. 229(2026) 108244]。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-07-01 Epub Date: 2026-06-01 DOI: 10.1016/j.phrs.2026.108272
Jingyi Yu, Sai Jiang, Yanan Wang, Hejing Pan, Hui Liu, Xuanlin Li, Yaolong Chen, Chengping Wen
{"title":"Corrigendum to “Placebo design, reporting compliance, and methodological problems in randomized, placebo-controlled trials of Chinese herbal medicine: A cross-sectional study” [Pharmacol. Res. 229 (2026) 108244]","authors":"Jingyi Yu,&nbsp;Sai Jiang,&nbsp;Yanan Wang,&nbsp;Hejing Pan,&nbsp;Hui Liu,&nbsp;Xuanlin Li,&nbsp;Yaolong Chen,&nbsp;Chengping Wen","doi":"10.1016/j.phrs.2026.108272","DOIUrl":"10.1016/j.phrs.2026.108272","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"229 ","pages":"Article 108272"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “From natural drug regulation to precise targeted intervention: Anti-heart failure mechanisms based on the reconstruction of calcium-lipid homeostasis via mitochondria-endoplasmic reticulum structural coupling” [Pharmacol. Res. (2026) 229 108259] “从天然药物调节到精确靶向干预：通过线粒体-内质网结构偶联重建钙-脂质稳态的抗心力衰竭机制”的勘误表[Pharmacol]。Res.(2026) 229[8259]。
IF 12.2 2区 医学
Pharmacological research Pub Date : 2026-07-01 Epub Date: 2026-06-11 DOI: 10.1016/j.phrs.2026.108286
Qin Zhang, Yi Wei, Haijing Li, Wei Wang, Yong Wang
{"title":"Corrigendum to “From natural drug regulation to precise targeted intervention: Anti-heart failure mechanisms based on the reconstruction of calcium-lipid homeostasis via mitochondria-endoplasmic reticulum structural coupling” [Pharmacol. Res. (2026) 229 108259]","authors":"Qin Zhang,&nbsp;Yi Wei,&nbsp;Haijing Li,&nbsp;Wei Wang,&nbsp;Yong Wang","doi":"10.1016/j.phrs.2026.108286","DOIUrl":"10.1016/j.phrs.2026.108286","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"229 ","pages":"Article 108286"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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