Drug Resistance Updates最新文献

{"title":"Modeling the epidemiologic impact of age-targeted vaccination for drug-resistant tuberculosis","authors":"Pei-Yao Zhai ,&nbsp;Zhi-Xian Chen ,&nbsp;Ting Jiang ,&nbsp;Jian Feng ,&nbsp;Bin Zhang ,&nbsp;Xiao Zang ,&nbsp;Yan-Lin Zhao ,&nbsp;Gang Qin","doi":"10.1016/j.drup.2024.101172","DOIUrl":"10.1016/j.drup.2024.101172","url":null,"abstract":"<div><div>This study used a calibrated mathematical model to evaluate age-specific tuberculosis (TB) vaccination strategies, for drug-resistant (DR)-TB management in China. Prioritizing elderly vaccination significantly reduced multidrug-resistant or rifampicin-resistant TB incidence and mortality, while avoiding the need for second-line treatment, offering a promising approach to mitigate DR-TB burden by 2050.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101172"},"PeriodicalIF":15.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMOD3 accelerated resistance to immunotherapy in KRAS-mutated pancreatic cancer through promoting autophagy-dependent degradation of ASCL4","authors":"Zhiwei He ,&nbsp;Dijie Zheng ,&nbsp;Futang Li ,&nbsp;Liwen Chen ,&nbsp;Changhao Wu ,&nbsp;Zhirui Zeng ,&nbsp;Chao Yu","doi":"10.1016/j.drup.2024.101171","DOIUrl":"10.1016/j.drup.2024.101171","url":null,"abstract":"<div><div>The high prevalence of KRAS mutations in pancreatic cancer (PC) is widely acknowledged and results in the resistance of targeted ferroptosis therapy and immunotherapy. Herein, via a CRISPR/Cas9 library screen, the effects of ferroptosis agonists were increased in KRAS-mutant PC cells upon knockout of tropomodulin 3 (TMOD3), while these effects were not observed in KRAS-wild-type cells. Increased levels of TMOD3 were found in PC tissues, particularly in those with KRAS mutations. The increase in TMOD3 expression was facilitated by KRAS via the ETS transcription factor ELK1. Liquid chromatography–mass spectrometry (LC/MS) showed that TMOD3 increased acyl-CoA synthetase long chain family member 4 (ACSL4) protein expression and fatty acid metabolism. Mechanistically, TMOD3 promoted F-actin polymerization, thereby facilitating the fusion of autophagosomes with lysosomes, increasing the degradation of the ACSL4 protein, and augmenting the ferroptosis-inducing effects of RSL3. These effects of TMOD3 were counteracted by the administration of cytochalasin, the removal of the α2 domain of TMOD3, or the introduction of a mutation at S71. Cangrelor, an FDA-approved drug, can target TMOD3. In a mouse model, the suppression of TMOD3 using cangrelor or gene silencing technology resulted in increased infiltration of CD8+ T cells into tumor tissues with KRAS mutations and exhibited a synergistic effect with the PD-1 antibody. In conclusion, TMOD3 was found to inhibit ferroptosis and induced the resistance to PD-1 antibody by facilitating the fusion of autophagosomes and lysosomes through the promotion of F-actin polymerization in KRAS-mutant PC. TMOD3 was identified as a novel target for PC therapy.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101171"},"PeriodicalIF":15.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionising infection control: building the next generation of phage banks","authors":"Braira Wahid,&nbsp;Muhammad Salman Tiwana,&nbsp;Akhtar Ali","doi":"10.1016/j.drup.2024.101143","DOIUrl":"10.1016/j.drup.2024.101143","url":null,"abstract":"<div><div>The escalating global burden of antimicrobial resistance (AMR) represents a critical public health challenge. This rise in antibiotic resistance is concomitant with heightened antibiotic consumption, with an estimated annual usage of 100,000 to 200,000 tons. A recent systematic review, which analysed data from 204 countries, reported that AMR was responsible for 4.95 million deaths in 2019 (<span><span>Murray et al., 2022</span></span>). The growing threat of AMR is imposing a significant financial burden on the global economy, with the CDC reporting an additional annual cost of $20 billion in the U.S. and €9 billion in Europe. The emerging field of bacteriophage therapy offers promising potential as a game-changer in the era of AMR. However, existing literature reveals numerous research gaps and technological challenges, including insufficient information on phage pharmacology, genomics, and a lack of preclinical and clinical data. In addition to conducting further research to address existing knowledge gaps, establishing phage banks in clinical facilities could be a transformative advancement in the fight against AMR.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101143"},"PeriodicalIF":15.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance","authors":"Yumin Wang ,&nbsp;Yongming Chen ,&nbsp;Junjing Zhang ,&nbsp;Yihui Yang ,&nbsp;Joshua S. Fleishman ,&nbsp;Yan Wang ,&nbsp;Jinhua Wang ,&nbsp;Jichao Chen ,&nbsp;Yuanfang Li ,&nbsp;Hongquan Wang","doi":"10.1016/j.drup.2023.101018","DOIUrl":"10.1016/j.drup.2023.101018","url":null,"abstract":"<div><p>Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role of copper and copper triggered cell death in the pathogenesis of cancers have attracted attentions. Cuproptosis has garnered enormous interest in cancer research communities because of its great potential for cancer therapy. Copper-based treatment exerts an inhibiting role in tumor growth and may open the door for the treatment of chemotherapy-insensitive tumors. In this review, we provide a critical analysis on copper homeostasis and the role of copper dysregulation in the development and progression of cancers. Then the core molecular mechanisms of cuproptosis and its role in cancer is discussed, followed by summarizing the current understanding of copper-based agents (copper chelators, copper ionophores, and copper complexes-based dynamic therapy) for cancer treatment. Additionally, we summarize the emerging data on copper complexes-based agents and copper ionophores to subdue tumor chemotherapy resistance in different types of cancers. We also review the small-molecule compounds and nanoparticles (NPs) that may kill cancer cells by inducing cuproptosis, which will shed new light on the development of anticancer drugs through inducing cuproptosis in the future. Finally, the important concepts and pressing questions of cuproptosis in future research that should be focused on were discussed. This review article suggests that targeting cuproptosis could be a novel antitumor therapy and treatment strategy to overcome cancer drug resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"72 ","pages":"Article 101018"},"PeriodicalIF":24.3,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623001012/pdfft?md5=1548387e09d3fd0e6bf9ad08efacb05f&pid=1-s2.0-S1368764623001012-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72365113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity","authors":"Sabina Ranjit ,&nbsp;Yao Wang ,&nbsp;Jingwen Zhu ,&nbsp;Satish B. Cheepala ,&nbsp;Erin G. Schuetz ,&nbsp;Woo Jung Cho ,&nbsp;Beisi Xu ,&nbsp;Camenzind G. Robinson ,&nbsp;Gang Wu ,&nbsp;Anjaparavanda.P. Naren ,&nbsp;John D. Schuetz","doi":"10.1016/j.drup.2023.101017","DOIUrl":"10.1016/j.drup.2023.101017","url":null,"abstract":"<div><p><span>The role of ABCC4<span>, an ATP-binding cassette transporter, in the process of platelet formation<span><span>, megakaryopoiesis, is unknown. Here, we show that ABCC4 is highly expressed in </span>megakaryocytes (MKs). Mining of public genomic data (ATAC-seq and genome wide chromatin interactions, Hi-C) revealed that key megakaryopoiesis transcription factors (TFs) interacted with ABCC4 regulatory elements and likely accounted for high ABCC4 expression in MKs. Importantly these genomic interactions for ABCC4 ranked higher than for genes with known roles in megakaryopoiesis suggesting a role for ABCC4 in megakaryopoiesis. We then demonstrate that ABCC4 is required for optimal platelet formation as </span></span></span><em>in vitro</em> differentiation of fetal liver derived MKs from <em>Abcc4</em>^<em>-/-</em><span><span> mice exhibited impaired proplatelet formation and polyploidization, features required for optimal megakaryopoiesis. Likewise, a human megakaryoblastic cell line, MEG-01 showed that acute ABCC4 inhibition markedly suppressed key processes in megakaryopoiesis and that these effects were related to reduced cAMP export and enhanced dissociation of a negative regulator of megakaryopoiesis, </span>protein kinase A (PKA) from ABCC4. PKA activity concomitantly increased after ABCC4 inhibition which was coupled with significantly reduced GATA-1 expression, a TF needed for optimal megakaryopoiesis. Further, ABCC4 protected MKs from 6-mercaptopurine (6-MP) as </span><em>Abcc4</em>^<em>-/-</em><span> mice show a profound reduction in MKs after 6-MP treatment. In total, our studies show that ABCC4 not only protects the MKs but is also required for maximal platelet production from MKs, suggesting modulation of ABCC4 function might be a potential therapeutic strategy to regulate platelet production.</span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"72 ","pages":"Article 101017"},"PeriodicalIF":24.3,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71524876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising role of protein arginine methyltransferases in overcoming anti-cancer drug resistance","authors":"Yongxia Zhu ,&nbsp;Tong Xia ,&nbsp;Da-Qian Chen ,&nbsp;Xia Xiong ,&nbsp;Lihong Shi ,&nbsp;Yueqi Zuo ,&nbsp;Hongtao Xiao ,&nbsp;Li Liu","doi":"10.1016/j.drup.2023.101016","DOIUrl":"10.1016/j.drup.2023.101016","url":null,"abstract":"<div><p>Drug resistance remains a major challenge in cancer treatment, necessitating the development of novel strategies to overcome it. Protein arginine methyltransferases (PRMTs) are enzymes responsible for epigenetic arginine methylation, which regulates various biological and pathological processes, as a result, they are attractive therapeutic targets for overcoming anti-cancer drug resistance. The ongoing development of small molecules targeting PRMTs has resulted in the generation of chemical probes for modulating most PRMTs and facilitated clinical treatment for the most advanced oncology targets, including PRMT1 and PRMT5. In this review, we summarize various mechanisms underlying protein arginine methylation and the roles of specific PRMTs in driving cancer drug resistance. Furthermore, we highlight the potential clinical implications of PRMT inhibitors in decreasing cancer drug resistance. PRMTs promote the formation and maintenance of drug-tolerant cells via several mechanisms, including altered drug efflux transporters, autophagy, DNA damage repair, cancer stem cell-related function, epithelial-mesenchymal transition, and disordered tumor microenvironment. Multiple preclinical and ongoing clinical trials have demonstrated that PRMT inhibitors, particularly PRMT5 inhibitors, can sensitize cancer cells to various anti-cancer drugs, including chemotherapeutic, targeted therapeutic, and immunotherapeutic agents. Combining PRMT inhibitors with existing anti-cancer strategies will be a promising approach for overcoming anti-cancer drug resistance. Furthermore, enhanced knowledge of the complex functions of arginine methylation and PRMTs in drug resistance will guide the future development of PRMT inhibitors and may help identify new clinical indications.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"72 ","pages":"Article 101016"},"PeriodicalIF":24.3,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623000997/pdfft?md5=dae9eb08f0fe7bb8498e7f075e72a6b5&pid=1-s2.0-S1368764623000997-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71506802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cisplatin-activated ERβ/DCAF8 positive feedback loop induces chemoresistance in non-small cell lung cancer via PTEN/Akt axis","authors":"Yumeng Hu ,&nbsp;Yongjie Xu ,&nbsp;Ting Zhang ,&nbsp;Qianying Han ,&nbsp;Li Li ,&nbsp;Mingyang Liu ,&nbsp;Ni Li ,&nbsp;Genze Shao","doi":"10.1016/j.drup.2023.101014","DOIUrl":"10.1016/j.drup.2023.101014","url":null,"abstract":"<div><p>High levels of the estrogen receptor β (ERβ) predict poor prognosis following platinum-containing adjuvant chemotherapies in patients with non-small cell lung cancer (NSCLC). However, the precise role of ERβ remains elusive. In this study, we demonstrated that targeting ERβ could significantly increase the cytotoxicity of cisplatin both <em>in vitro</em> and <em>in vivo</em>. Mechanically, cisplatin directly binds to ERβ, which facilitates its homodimerization and nuclear translocation. ERβ activation transcriptionally represses the expression of DCAF8, an adaptor of CRL4 E3 ubiquitin ligase, which in turn attenuates the proteasomal degradation of ERβ, leading to ERβ accumulation; this positive feedback loop results in Akt activation and eventually cisplatin resistance in NSCLC through PTEN inhibition. Moreover, low expression of DCAF8 and high expression of ERβ are associated with treatment resistance in patients receiving cisplatin-containing adjuvant chemotherapy. The present results provide insights into the underlying mechanism of ERβ-induced cisplatin resistance and offer an alternative therapeutic strategy to improve the efficacy of platinum-based chemotherapy in patients with NSCLC.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"71 ","pages":"Article 101014"},"PeriodicalIF":24.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623000973/pdfft?md5=1ba5c55c3c16b76c7d4ea4ab915611d3&pid=1-s2.0-S1368764623000973-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic failure: Beyond antimicrobial resistance","authors":"Cesar de la Fuente-Nunez ,&nbsp;Angela Cesaro ,&nbsp;Robert E.W. Hancock","doi":"10.1016/j.drup.2023.101012","DOIUrl":"10.1016/j.drup.2023.101012","url":null,"abstract":"<div><p>Despite significant progress in antibiotic discovery, millions of lives are lost annually to infections. Surprisingly, the failure of antimicrobial treatments to effectively eliminate pathogens frequently cannot be attributed to genetically-encoded antibiotic resistance. This review aims to shed light on the fundamental mechanisms contributing to clinical scenarios where antimicrobial therapies are ineffective (i.e., antibiotic failure), emphasizing critical factors impacting this under-recognized issue. Explored aspects include biofilm formation and sepsis, as well as the underlying microbiome. Therapeutic strategies beyond antibiotics, are examined to address the dimensions and resolution of antibiotic failure, actively contributing to this persistent but escalating crisis. We discuss the clinical relevance of antibiotic failure beyond resistance, limited availability of therapies, potential of new antibiotics to be ineffective, and the urgent need for novel anti-infectives or host-directed therapies directly addressing antibiotic failure. Particularly noteworthy is multidrug adaptive resistance in biofilms that represent 65 % of infections, due to the lack of approved therapies. Sepsis, responsible for 19.7 % of all deaths (as well as severe COVID-19 deaths), is a further manifestation of this issue, since antibiotics are the primary frontline therapy, and yet 23 % of patients succumb to this condition.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"71 ","pages":"Article 101012"},"PeriodicalIF":24.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress","authors":"Yuanjun Lu ,&nbsp;Yau-Tuen Chan ,&nbsp;Junyu Wu ,&nbsp;Zixin Feng ,&nbsp;Hongchao Yuan ,&nbsp;Qiucheng Li ,&nbsp;Tingyuan Xing ,&nbsp;Lin Xu ,&nbsp;Cheng Zhang ,&nbsp;Hor-Yue Tan ,&nbsp;Terence Kin-Wah Lee ,&nbsp;Yibin Feng ,&nbsp;Ning Wang","doi":"10.1016/j.drup.2023.101015","DOIUrl":"10.1016/j.drup.2023.101015","url":null,"abstract":"<div><h3>Aims</h3><p>Therapeutic outcome of sorafenib in hepatocellular carcinoma (HCC) is undermined by the development of drug resistance. This study aimed to identify the critical microRNA (miRNA) which is responsible for sorafenib resistance at the genomic level.</p></div><div><h3>Methods</h3><p>CRISPR/Cas9 screen followed by gain- and loss-of-function assays both in vitro and in vivo were applied to identify the role of miR-3689a-3p in mediating sorafenib response in HCC. The upstream and downstream molecules of miR-3689a-3p and their mechanism of action were investigated.</p></div><div><h3>Results</h3><p>CRISPR/Cas9 screening identified miR-3689a-3p was the most up-regulated miRNA in sorafenib sensitive HCC. Knockdown of miR-3689a-3p significantly increased sorafenib resistance, while its overexpression sensitized HCC response to sorafenib treatment. Proteomic analysis revealed that the effect of miR-3689a-3p was related to the copper-dependent mitochondrial superoxide dismutase type 1 (SOD1) activity. Mechanistically, miR-3689a-3p targeted the 3′UTR of the intracellular copper chaperone for superoxide dismutase (CCS) and suppressed its expression. As a result, miR-3689a-3p disrupted the intracellular copper trafficking and reduced SOD1-mediated scavenge of mitochondrial oxidative stress that eventually caused HCC cell death in response to sorafenib treatment. CCS overexpression blunted sorafenib response in HCC. Clinically, miR-3689a-3p was down-regulated in HCC and predicted favorable prognosis for HCC patients.</p></div><div><h3>Conclusion</h3><p>Our findings provide comprehensive evidence for miR-3689a-3p as a positive regulator and potential druggable target for improving sorafenib treatment in HCC.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"71 ","pages":"Article 101015"},"PeriodicalIF":24.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623000985/pdfft?md5=982d54e6910730144d4b28c322e91148&pid=1-s2.0-S1368764623000985-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance","authors":"Huize Shen ,&nbsp;Rui Zhu ,&nbsp;Yanyang Liu ,&nbsp;Yangjian Hong ,&nbsp;Jiaming Ge ,&nbsp;Jie Xuan ,&nbsp;Wenyuan Niu ,&nbsp;Xuefei Yu ,&nbsp;Jiang-Jiang Qin ,&nbsp;Qinglin Li","doi":"10.1016/j.drup.2023.101013","DOIUrl":"10.1016/j.drup.2023.101013","url":null,"abstract":"<div><p>Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"72 ","pages":"Article 101013"},"PeriodicalIF":24.3,"publicationDate":"2023-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623000961/pdfft?md5=ea36196d0d2fa25a8ef3b2b8f13f4d5a&pid=1-s2.0-S1368764623000961-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71506790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}