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Emergence of novel Klebsiella pneumoniae ST types with multidrug resistance in clinic Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-23 Zhenghao Lou, Xiaolu Yang, Yu Yang, Kexin Guo, Lu Gong, Hao Xu, Beiwen Zheng, Wenhong Liu, Mantao Chen, Xiawei Jiang
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O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-12 Xiangbo Zeng, Zhiliang Chen, Yuanchao Zhu, Lei Liu, Zhiyong Zhang, Yongyuan Xiao, Qiong Wang, Shiyu Pang, Fengjin Zhao, Bihong Xu, Mengxin Leng, Xiaocen Liu, Chenxi Hu, Siying Zeng, Fei Li, Wenlian Xie, Wanlong Tan, Zaosong Zheng
Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive
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RGS5+ lymphatic endothelial cells facilitate metastasis and acquired drug resistance of breast cancer through oxidative stress-sensing mechanism Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-06 Caixin Qiu, Chaoyi Tang, Yujun Tang, Ka Su, Xiao Chai, Zexu Zhan, Xing Niu, Jiehua Li
Oxidative stress reflected by elevated reactive oxygen species (ROS) in the tumor ecosystem, is a hallmark of human cancers. The mechanisms by which oxidative stress regulate the metastatic ecosystem and resistance remain elusive. This study aimed to dissect the oxidative stress-sensing machinery during the evolvement of early dissemination and acquired drug resistance in breast cancer.
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The important role of lactylation in regulating DNA damage repair and tumor chemotherapy resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-06 Jia Li, Zhe-Sheng Chen, Yihang Pan, Leli Zeng
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Plasmid-borne tigecycline resistance gene tet(X4) in Salmonella enterica and Escherichia coli isolates from a pediatric patient with diarrhea Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-02 Zelin Yan, Yan Li, Yingling Ni, Xiaoni Xia, Yanyan Zhang, Yuchen Wu, Jing Zhang, Gongxiang Chen, Ruichao Li, Rong Zhang
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Mechanism of staphylococcal resistance to clinically relevant antibiotics Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-31 Daniela Brdová, Tomáš Ruml, Jitka Viktorová
, a notorious pathogen with versatile virulence, poses a significant challenge to current antibiotic treatments due to its ability to develop resistance mechanisms against a variety of clinically relevant antibiotics. In this comprehensive review, we carefully dissect the resistance mechanisms employed by against various antibiotics commonly used in clinical settings. The article navigates through
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Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-30 Ashu Shah, Koelina Ganguly, Sanchita Rauth, Shamema S. Sheree, Imran Khan, Apar K. Ganti, Moorthy P. Ponnusamy, Sushil Kumar, Maneesh Jain, Surinder K. Batra
Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic
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Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-24 Shin-Chih Lin, Ya-Chuan Tsai, Ying-Lan Chen, Hui-Kuan Lin, Yun-Chen Huang, Yi-Syuan Lin, Yu-Sheng Cheng, Hsing-Yi Chen, Chia-Jung Li, Tsung-Yen Lin, Shih-Chieh Lin
The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant
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CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-24 Gong Li, Teng-Fei Long, Shi-Ying Zhou, Li-Juan Xia, Ang Gao, Lei Wan, Xiao-Yuan Diao, Yu-Zhang He, Ruan-Yang Sun, Jin-Tao Yang, Sheng-Qiu Tang, Hao Ren, Liang-Xing Fang, Xiao-Ping Liao, Ya-Hong Liu, Liang Chen, Jian Sun
The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer
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Revolutionising infection control: building the next generation of phage banks Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-22 Braira Wahid, Muhammad Salman Tiwana, Akhtar Ali
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Fusion event mediated by IS903B between chromosome and plasmid in two MCR-9- and KPC-2-co-producing Klebsiella pneumoniae isolates Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-17 Ruishan Liu, Yingying Chen, Hao Xu, Huanran Zhang, Yi Liu, Xiaojing Liu, Haowei Ye, Mantao Chen, Beiwen Zheng
Herein, we first isolated two MCR-9- and KPC-2-co-producing isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.
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Unraveling the secrets: Evolution of resistance mediated by membrane proteins Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-16 Xue Yang, Min Li, Zi-Chang Jia, Yan Liu, Shun-Fan Wu, Mo-Xian Chen, Ge-Fei Hao, Qing Yang
Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand
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Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-16 Hui Li, Yao Chen, Ming Ding, Jingjing Liu, Huiying Sun, Houshun Fang, Samuel W. Brady, Yan Xu, Fabian Glaser, Xiaotu Ma, Yabin Tang, Liang Du, Xiaoyu Wu, Shuxuan Wang, Liang Zhu, Benshang Li, Shuhong Shen, Jinghui Zhang, Liang Zheng, Jiyang Yu, Yehuda G. Assaraf, Bin-Bing S. Zhou
The antifolate methotrexate (MTX) is an anchor drug used in acute lymphoblastic leukemia (ALL) with poorly understood chemoresistance mechanisms in relapse. Herein we find decreased folate polyglutamylation network activities and inactivating FPGS mutations, both of which could induce MTX resistance and folate metabolic vulnerability in relapsed ALL.
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Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-16 Xueqing Wu, Babek Alibayov, Xi Xiang, Santiago M. Lattar, Fuminori Sakai, Austin A. Medders, Brenda S. Antezana, Lance E. Keller, Ana G.J. Vidal, Yih-Ling Tzeng, D. Ashley Robinson, David S. Stephens, Yunsong Yu, Jorge E. Vidal
To investigate the molecular events associated with acquiring macrolide resistance genes [/ (Mega) or ] in () during nasopharyngeal colonization. Genomic analysis of 128 macrolide-resistant isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn-related elements. Studies using confocal and electron microscopy demonstrated that during
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The key role of iroBCDN-lacking pLVPK-like plasmid in the evolution of the most prevalent hypervirulent carbapenem-resistant ST11-KL64 Klebsiella pneumoniae in China Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-14 Xinmiao Jia, Ying Zhu, Peiyao Jia, Cuidan Li, Xiaobing Chu, Tianshu Sun, Xiaoyu Liu, Wei Yu, Fei Chen, Yingchun Xu, Qiwen Yang
Hypervirulent carbapenem-resistant (hv-CRKP), coharboring hypervirulence and carbapenem-resistance genes mediated by plasmids, causes infections with extremely high mortality and seriously impacts public health. Exploring the transfer mechanisms of virulence/carbapenem-resistance plasmids, as well as the formation and evolution pathway of hv-CRKP is of great significance to the control of hv-CRKP infections
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CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-12 Yunru Gu, Tingting Xu, Yuan Fang, Jun Shao, Tong Hu, Xi Wu, Haoyang Shen, Yangyue Xu, Jingxin Zhang, Yu Song, Yang Xia, Yongqian Shu, Pei Ma
As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance
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Editorial: ABC transporters and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-10 Qisi Lu, Suresh V. Ambudkar, Dong-Hua Yang
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Functional relay between Mph(A) enzyme and Mrx efflux pump mediates azithromycin resistance, a novel mechanism of bacterial antimicrobial resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-08 Xuemei Yang, Haoshuai Zhang, Yang Tang, Heng Heng, Yan-Chu Cheung, Xuejiao Song, Hang-Kin Kong, Edward Wai-Chi Chan, Sheng Chen
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crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-06 Yutian Zou, Anli Yang, Bo Chen, Xinpei Deng, Jindong Xie, Danian Dai, Jinhui Zhang, Hailin Tang, Tao Wu, Zhigang Zhou, Xiaoming Xie, Jin Wang
With the wide application of trastuzumab deruxtecan (T-DXd), the survival of HER2-low breast cancer patients is dramatically improved. However, resistance to T-DXd still exists in a subset of patients, and the molecular mechanism remains unclear. An shRNA lentiviral library functional screening was performed to identify potential circular RNA (crRNA) that mediates T-DXd resistance. RNA pull-down, mass
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Cellular and molecular mechanisms of gastrointestinal cancer liver metastases and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-06 Daosong Dong, Xue Yu, Jingjing Xu, Na Yu, Zhe Liu, Yanbin Sun
Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth
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An increased prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae associated with the COVID-19 pandemic Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-02 Chao Liu, Jun Guo, Shuaihua Fan, Wei Guo, Huaiqing Qi, Stephen Baker, Pengcheng Du, Bin Cao
(Kp) is a common community-acquired and nosocomial pathogen. Carbapenem-resistant and hypervirulent (CR-hvKp) variants can emerge rapidly within healthcare facilities and impacted by other infectious agents such as COVID-19 virus. To understand the impact of COVID-19 virus on the prevalence of CR-hvKp, we accessed Kp genomes with corresponding metadata from GenBank. Sequence types (STs), antimicrobial
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Emergence of silent NDM-1 carbapenemase gene in carbapenem-susceptible Klebsiella pneumoniae: Clinical implications and epidemiological insights Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-29 Juanxiu Qin, Yuan Zhu, Yiwei Zhu, Qianqian Gao, Haomin Zhang, Min Li, Zhen Shen
The global dissemination of carbapenemase genes, particularly , poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent in a cluster of clonally related carbapenem-susceptible strains from a single patient. Despite initial
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Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-27 Yufei Lan, Xiaodie Li, Boyang Liu, Jiankun Lu, Boming Zuo, Yue Wang, Shuting Cao, Xin Fu, Qu Yue, Xin Luo, Xiangyang Zhong, Yaoyuan Dong, Zhao Wang, Tao Yang, Xinyun Xie, Tianci Zeng, Manqing Zhang, Yuankai Wang, Yixiong Shen, Huaqin Zuo, Yan Zhao, Chao Zhang, Hongbo Guo
O-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed
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BCL7A inhibits the progression and drug-resistance in acute myeloid leukemia Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-22 Tushuai Li, Renjie Gao, Kaiwen Xu, Pengpeng Pan, Congcong Chen, Daokuan Wang, Keyi Zhang, Jilei Qiao, Yue Gu
This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on cancer progression and drug resistance. BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with
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Intersecting pathways: The role of hybrid E/M cells and circulating tumor cells in cancer metastasis and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-14 Amirali Hariri, Mina Mirian, Arezoo Khosravi, Atefeh Zarepour, Siavash Iravani, Ali Zarrabi
Cancer metastasis and therapy resistance are intricately linked with the dynamics of Epithelial-Mesenchymal Transition (EMT) and Circulating Tumor Cells (CTCs). EMT hybrid cells, characterized by a blend of epithelial and mesenchymal traits, have emerged as pivotal in metastasis and demonstrate remarkable plasticity, enabling transitions across cellular states crucial for intravasation, survival in
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Targeting undruggable phosphatase overcomes trastuzumab resistance by inhibiting multi-oncogenic kinases Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-14 Lu Wang, Yusheng Lin, Zhimeng Yao, Nipun Babu, Wan Lin, Chaoying Chen, Liang Du, Songwang Cai, Yunlong Pan, Xiao Xiong, Qiantao Ye, Hongzheng Ren, Dianzheng Zhang, Yexi Chen, Sai-Ching Jim Yeung, Edwin Bremer, Hao Zhang
Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2 cancers. The role of protein tyrosine phosphatases (PTPs) in trastuzumab resistance is not well understood. In this study, we aim to identify pivotal PTPs affecting trastuzumab resistance and devise a novel counteracting strategy. Four public
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Point mutation P174L of the penA gene endowing ceftazidime resistance to Burkholderia pseudomallei in China Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-14 Shen Tian, Xingyong Wu, Lin Liu, Anyang Li, Xuemiao Li, Hua Pei, Yanshuang Wang, David A.B. Dance, Hai Chen, Qianfeng Xia
In a clinical isolate of from Hainan, the association between the emergence of ceftazidime resistance and a novel PenA P174L allele was identified for the first time, providing an understanding of one mechanism by which ceftazidime resistance arises in .
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Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-10 Kang Ma, Shi Wang, Yingjie Ma, Lan Zeng, Kai Xu, Ning Mu, Ying Lai, Yaning Shi, Chuanyan Yang, Beike Chen, Yulian Quan, Lan Li, Yongling Lu, Yang Yang, Yan Liu, Rong Hu, Xiaoming Wang, Yujie Chen, Xiuwu Bian, Hua Feng, Fei Li, Tunan Chen
Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically
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Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-06 Wei-Feng Hong, Feng Zhang, Nan Wang, Jun-Ming Bi, Ding-Wen Zhang, Lu-Sheng Wei, Zhen-Tao Song, Gordon B. Mills, Min-Min Chen, Xue-Xin Li, Shi-Suo Du, Min Yu
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully
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A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-03 Jinan Guo, Xiaoshi Ma, Dongcheng Liu, Fei Wang, Jinquan Xia, Bin Zhang, Pan Zhao, Fuhua Zhong, Lipeng Chen, Qiaoyun Long, Lu Jiang, Siyu Zhang, Naikai Liao, Jigang Wang, Weiqing Wu, Jichao Sun, Mou Huang, Zhiqiang Cheng, Guixiao Huang, Chang Zou
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Circulating tumor cells with increasing aneuploidy predict inferior prognosis and therapeutic resistance in small cell lung cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-02 Zhongpeng Xie, Yanxia Wang, Tingfei Chen, Wei Fan, Lihong Wei, Bixia Liu, Xiaohua Situ, Qinru Zhan, Tongze Fu, Tian Tian, Shuhua Li, Qiong He, Jianwen Zhou, Huipin Wang, Juan Du, Hsian-Rong Tseng, Yiyan Lei, Ke-Jing Tang, Zunfu Ke
Treatment resistance commonly emerges in small cell lung cancer (SCLC), necessitating the development of novel and effective biomarkers to dynamically assess therapeutic efficacy. This study aims to evaluate the clinical utility of aneuploid circulating tumor cells (CTCs) for risk stratification and treatment response monitoring. A total of 126 SCLC patients (two cohorts) from two independent cancer
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Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-25 Antonino Glaviano, Seth A. Wander, Richard D. Baird, Kenneth C.-H. Yap, Hiu Yan Lam, Masakazu Toi, Daniela Carbone, Birgit Geoerger, Violeta Serra, Robert H. Jones, Joanne Ngeow, Eneda Toska, Justin Stebbing, Karen Crasta, Richard S. Finn, Patrizia Diana, Karla Vuina, Robertus A.M. de Bruin, Uttam Surana, Aditya Bardia, Alan Prem Kumar
Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain
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Intercellular adhesion molecule-1 suppresses TMZ chemosensitivity in acquired TMZ-resistant gliomas by increasing assembly of ABCB1 on the membrane Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-24 Xin Zhang, Yingying Tan, Tao Li, Dashan Tan, Bin Fu, Mengdi Yang, Yaxin Chen, Mengran Cao, Chenyuan Xuan, Qianming Du, Rong Hu, Qing Wang
Despite aggressive treatment, the recurrence of glioma is an inevitable occurrence, leading to unsatisfactory clinical outcomes. A plausible explanation for this phenomenon is the phenotypic alterations that glioma cells undergo aggressive therapies, such as TMZ-therapy. However, the underlying mechanisms behind these changes are not well understood. The TMZ chemotherapy resistance model was employed
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Cancer plasticity in therapy resistance: Mechanisms and novel strategies Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-22 Xing Niu, Wenjing Liu, Yinling Zhang, Jing Liu, Jianjun Zhang, Bo Li, Yue Qiu, Peng Zhao, Zhongmiao Wang, Zhe Wang
Therapy resistance poses a significant obstacle to effective cancer treatment. Recent insights into cell plasticity as a new paradigm for understanding resistance to treatment: as cancer progresses, cancer cells experience phenotypic and molecular alterations, corporately known as cell plasticity. These alterations are caused by microenvironment factors, stochastic genetic and epigenetic changes, and/or
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Corrigendum to: “Circumventing drug resistance in gastric cancer: A spatial multi-omics exploration of chemo and immuno-therapeutic response dynamics” [Drug Resist Updates 74 (2024) 101080] Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-19 Gang Che, Jie Yin, Wankun Wang, Yandong Luo, Yiran Chen, Xiongfei Yu, Haiyong Wang, Xiaosun Liu, Zhendong Chen, Xing Wang, Yu Chen, Xujin Wang, Kaicheng Tang, Jiao Tang, Wei Shao, Chao Wu, Jianpeng Sheng, Qing Li, Jian Liu
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Surface chemistry engineered selenium nanoparticles as bactericidal and immuno-modulating dual-functional agents for combating methicillin-resistant Staphylococcus aureus Infection Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-15 Qingyue Bu, Dan Jiang, Yangyang Yu, Yunqing Deng, Tianfeng Chen, Ligeng Xu
Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS)
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LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-14 Kai-Lin Chen, Sai-Wei Huang, Ji-Jin Yao, Shi-Wei He, Sha Gong, Xi-Rong Tan, Ye-Lin Liang, Jun-Yan Li, Sheng-Yan Huang, Ying-Qin Li, Yin Zhao, Han Qiao, Sha Xu, Shengbing Zang, Jun Ma, Na Liu
Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated
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Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-04 Ning Ji, Hui Li, Yixuan Zhang, Yuelin Li, Peiyu Wang, Xin Chen, Yi-Nan Liu, Jing-Quan Wang, Yuqi Yang, Zhe-Sheng Chen, Yueguo Li, Ran Wang, Dexin Kong
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Targeting anoikis resistance as a strategy for cancer therapy Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-01 Yumin Wang, Sihang Cheng, Joshua S. Fleishman, Jichao Chen, Hailin Tang, Zhe-Sheng Chen, Wenkuan Chen, Mingchao Ding
Anoikis, known as matrix detachment-induced apoptosis or detachment-induced cell death, is crucial for tissue development and homeostasis. Cancer cells develop means to evade anoikis, e.g. anoikis resistance, thereby allowing for cells to survive under anchorage-independent conditions. Uncovering the mechanisms of anoikis resistance will provide details about cancer metastasis, and potential strategies
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Application of biomimetic nanovaccines in cancer immunotherapy: A useful strategy to help combat immunotherapy resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-06-01 Zhijie Xu, Haiyan Zhou, Tongfei Li, Qiaoli Yi, Abhimanyu Thakur, Kui Zhang, Xuelei Ma, Jiang-Jiang Qin, Yuanliang Yan
Breakthroughs in actual clinical applications have begun through vaccine-based cancer immunotherapy, which uses the body's immune system, both humoral and cellular, to attack malignant cells and fight diseases. However, conventional vaccine approaches still face multiple challenges eliciting effective antigen-specific immune responses, resulting in immunotherapy resistance. In recent years, biomimetic
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CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-05-28 Jiatong Lin, Zejian Lyu, Huolun Feng, Huajie Xie, Jingwen Peng, Weifu Zhang, Jun Zheng, Jiabin Zheng, Zihao Pan, Yong Li
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FAT1 as a tumor mutation burden specific gene affects the immunotherapy effect in head and neck squamous cell cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-05-27 Haotian Cao, Tianjun Lan, Shijia Kuang, Liansheng Wang, Jintao Li, Qunxin Li, Yanyan Li, Qiuping Xu, Qian Chen, Shuwei Ren, Chunhong Lan, Nengtai Ouyang, Jianwei Liao, Yongsheng Huang, Jinsong Li
Response to immunotherapy is the main challenge of head and neck squamous cancer (HNSCC) treatment. Previous studies have indicated that tumor mutational burden (TMB) is associated with prognosis, but it is not always a precise index. Hence, investigating specific genetic mutations and tumor microenvironment (TME) changes in TMB-high patients is essential for precision therapy of HNSCC. A total of
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KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression Drug Resist. Updat. (IF 15.8) Pub Date : 2024-05-27 Hao Zhang, Yujia Zheng, Zhen Wang, Lin Dong, Liyan Xue, Xiaolin Tian, Haiteng Deng, Qi Xue, Shugeng Gao, Yibo Gao, Chunxiang Li, Jie He
Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance
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Characterization of NMCR-3, NMCR-4 and NMCR-5, three novel non-mobile colistin resistance determinants: Implications for MCR-3, MCR-7, and MCR-5 progenitors, respectively Drug Resist. Updat. (IF 15.8) Pub Date : 2024-04-26 Yating Guo, Geng Zou, Anusak Kerdsin, Constance Schultsz, Can Hu, Weicheng Bei, Huanchun Chen, Jinquan Li, Yang Zhou
In this study, the progenitors of MCR-3, MCR-7 and MCR-5, namely NMCR-3, NMCR-4 and NMCR-5, were firstly discovered and indicating was a natural reservoir for MCR-3 and MCR-7. Furthermore, different evolutionary models for MCR-3, MCR-7 and MCR-5 were proposed.
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Heterogeneity of SOS response expression in clinical isolates of Escherichia coli influences adaptation to antimicrobial stress Drug Resist. Updat. (IF 15.8) Pub Date : 2024-04-23 Sara Diaz-Diaz, Andrea Garcia-Montaner, Roberta Vanni, Marina Murillo-Torres, Esther Recacha, Marina R. Pulido, Maria Romero-Muñoz, Fernando Docobo-Pérez, Alvaro Pascual, Jose Manuel Rodriguez-Martinez
In recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of on response to the fluoroquinolone, ciprofloxacin. analysis of whole genome sequencing data showed remarkable sequence conservation
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Spotlight on ideal target antigens and resistance in antibody-drug conjugates: Strategies for competitive advancement Drug Resist. Updat. (IF 15.8) Pub Date : 2024-04-23 Mingxia Jiang, Qiao Li, Binghe Xu
Antibody-drug conjugates (ADCs) represent a novel and promising approach in targeted therapy, uniting the specificity of antibodies that recognize specific antigens with payloads, all connected by the stable linker. These conjugates combine the best targeted and cytotoxic therapies, offering the killing effect of precisely targeting specific antigens and the potent cell-killing power of small molecule
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Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy Drug Resist. Updat. (IF 15.8) Pub Date : 2024-04-16 Qin Zhou, Xinyi Tu, Xiaonan Hou, Jia Yu, Fei Zhao, Jinzhou Huang, Jake Kloeber, Anna Olson, Ming Gao, Kuntian Luo, Shouhai Zhu, Zheming Wu, Yong Zhang, Chenyu Sun, Xiangyu Zeng, Kenneth J. Schoolmeester, John S. Weroha, Xiwen Hu, Yanxia Jiang, Liewei Wang, Robert W. Mutter, Zhenkun Lou
Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression
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Potential targets and therapeutics for cancer stem cell-based therapy against drug resistance in hepatocellular carcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-04-16 Hongxing Zhao, Yuhang Ling, Jie He, Jinling Dong, Qinliang Mo, Yao Wang, Ying Zhang, Hongbin Yu, Chengwu Tang
Hepatocellular carcinoma (HCC) is the most common digestive malignancyin the world, which is frequently diagnosed at late stage with a poor prognosis. For most patients with advanced HCC, the therapeutic options arelimiteddue to cancer occurrence of drug resistance. Hepatic cancer stem cells (CSCs) account for a small subset of tumor cells with the ability of self-renewal and differentiationin HCC
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Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-29 Qi Wang, Ruobing Wang, Shuyi Wang, Anru Zhang, Qiaoyan Duan, Shijun Sun, Longyang Jin, Xiaojuan Wang, Yawei Zhang, Chunlei Wang, Haiquan Kang, Zhijie Zhang, Kang Liao, Yinghui Guo, Liang Jin, Zhiwu Liu, Chunxia Yang, Hui Wang, on behalf of the China Carbapenem-Resistant Enterobacterales (CRE) Network
Carbapenem-resistant (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology
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Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-26 Yuxian Huang, Yinjie Qin, Yingzhi He, Dezhi Qiu, Yeqin Zheng, Jiayue Wei, Lenghe Zhang, Dong‑Hua Yang, Yuhua Li
Molecular targeted drugs and chimeric antigen receptor (CAR) T cell therapy represent specific biological treatments that have significantly improved the efficacy of treating hematologic malignancies. However, they face challenges such as drug resistance and recurrence after treatment. Combining molecular targeted drugs and CAR-T cells could regulate immunity, improve tumor microenvironment (TME),
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Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-19 Alberto Diaz-Jimenez, Maria Ramos, Barbara Helm, Sara Chocarro, Dario Lucas Frey, Shubham Agrawal, Kalman Somogyi, Ursula Klingmüller, Junyan Lu, Rocio Sotillo
Precision oncology has revolutionized the treatment of ALK-positive lung cancer with targeted therapies. However, an unmet clinical need still to address is the treatment of refractory tumors that contain drug-induced resistant mutations in the driver oncogene or exhibit resistance through the activation of diverse mechanisms. In this study, we established mouse tumor-derived cell models representing
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Circumventing drug resistance in gastric cancer: A spatial multi-omics exploration of chemo and immuno-therapeutic response dynamics Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-19 Gang Che, Jie Yin, Wankun Wang, Yandong Luo, Yiran Chen, Xiongfei Yu, Haiyong Wang, Xiaosun Liu, Zhendong Chen, Xing Wang, Yu Chen, Xujin Wang, Kaicheng Tang, Jiao Tang, Wei Shao, Chao Wu, Jianpeng Sheng, Qing Li, Jian Liu
Gastric Cancer (GC) characteristically exhibits heterogeneous responses to treatment, particularly in relation to immuno plus chemo therapy, necessitating a precision medicine approach. This study is centered around delineating the cellular and molecular underpinnings of drug resistance in this context. We undertook a comprehensive multi-omics exploration of postoperative tissues from GC patients undergoing
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Targeted dual degradation of HER2 and EGFR obliterates oncogenic signaling, overcomes therapy resistance, and inhibits metastatic lesions in HER2-positive breast cancer models Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-13 Lu Yang, Arup Bhattacharya, Darrell Peterson, Yun Li, Xiaozhuo Liu, Elisabetta Marangoni, Valentina Robila, Yuesheng Zhang
Human epidermal growth factor receptor 2 (HER2) is an oncogenic receptor tyrosine kinase amplified in approximately 20% of breast cancer (BC). HER2-targeted therapies are the linchpin of treating HER2-positive BC. However, drug resistance is common, and the main resistance mechanism is unknown. We tested the hypothesis that drug resistance results mainly from inadequate or lack of inhibition of HER2
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TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770–5p axis in PDAC Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-12 Wenjie Huang, Xiaojun Hu, Xiang He, Dongyue Pan, Zhaorong Huang, Zhanfeng Gu, Guobing Huang, Ping Wang, Chunhui Cui, Yingfang Fan
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. The clinical significance of Tripartite Motif Containing 29 (TRIM29)
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A novel SIK2 inhibitor SIC-19 exhibits synthetic lethality with PARP inhibitors in ovarian cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-03-06 Fang Wang, Xuejiao Yu, Jun Qian, Yumin Cao, Shunli Dong, Shenghua Zhan, Zhen Lu, Robert C. Bast Jr., Qingxia Song, Youguo Chen, Yi Zhang, Jinhua Zhou
Ovarian cancer patients with HR proficiency (HRP) have had limited benefits from PARP inhibitor treatment, highlighting the need for improved therapeutic strategies. In this study, we developed a novel SIK2 inhibitor, SIC-19, and investigated its potential to enhance the sensitivity and expand the clinical utility of PARP inhibitors in ovarian cancer. The SIK2 protein was modeled using a Molecular
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Solving the antibacterial resistance in Europe: The multipronged approach of the COST Action CA21145 EURESTOP Drug Resist. Updat. (IF 15.8) Pub Date : 2024-02-17 Carole Seguin-Devaux, Tomislav Mestrovic, Jacobus J. Arts, Didem Sen Karaman, Cristina Nativi, Dana Reichmann, Priyanka Sahariah, Younes Smani, Patricia Rijo, Mattia Mori, on behalf of the COST Action CA21145 EURESTOP
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Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy Drug Resist. Updat. (IF 15.8) Pub Date : 2024-02-13 Binglei Zhang, Jianxiang Shi, Xiaojing Shi, Xiaolu Xu, Le Gao, Song Li, Mengmeng Liu, Mengya Gao, Shuiling Jin, Jian Zhou, Dandan Fan, Fang Wang, Zhenyu Ji, Zhilei Bian, Yongping Song, Wenzhi Tian, Yichao Zheng, Linping Xu, Wei Li
The treatment for trastuzumab-resistant breast cancer (BC) remains a challenge in clinical settings. It was known that CD47 is preferentially upregulated in HER2 BC cells, which is correlated with drug resistance to trastuzumab. Here, we developed a novel anti-CD47/HER2 bispecific antibody (BsAb) against trastuzumab-resistant BC, named IMM2902. IMM2902 demonstrated high binding affinity, blocking activity
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AI in infectious diseases: The role of datasets Drug Resist. Updat. (IF 15.8) Pub Date : 2024-02-10 C, e, s, a, r, , d, e, , l, a, , F, u, e, n, t, e, -, N, u, n, e, z
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Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-02-06 Tomoka Gose, Ali Rasouli, Sepehr Dehghani-Ghahnaviyeh, Po-Chao Wen, Yao Wang, John Lynch, Yu Fukuda, Talha Shafi, Robert C. Ford, Emad Tajkhorshid, John D. Schuetz
ABCG2 is an important ATP-binding cassette transporter impacting the absorption and distribution of over 200 chemical toxins and drugs. ABCG2 also reduces the cellular accumulation of diverse chemotherapeutic agents. Acquired somatic mutations in the phylogenetically conserved amino acids of ABCG2 might provide unique insights into its molecular mechanisms of transport. Here, we identify a tumor-derived
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ABCB1-dependent collateral sensitivity of multidrug-resistant colorectal cancer cells to the survivin inhibitor MX106-4C Drug Resist. Updat. (IF 15.8) Pub Date : 2024-02-06 Zi-Ning Lei, Najah Albadari, Qiu-Xu Teng, Hadiar Rahman, Jing-Quan Wang, Zhongzhi Wu, Dejian Ma, Suresh V. Ambudkar, John N.D. Wurpel, Yihang Pan, Wei Li, Zhe-Sheng Chen
To investigate the collateral sensitivity (CS) of ABCB1-positive multidrug resistant (MDR) colorectal cancer cells to the survivin inhibitor MX106–4C and the mechanism. Biochemical assays (MTT, ATPase, drug accumulation/efflux, Western blot, RT-qPCR, immunofluorescence, flow cytometry) and bioinformatic analyses (mRNA-sequencing, reversed-phase protein array) were performed to investigate the hypersensitivity