-
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 24.3) 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
-
TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC Drug Resist. Updat. (IF 24.3) 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)
-
A Novel SIK2 Inhibitor SIC-19 exhibits Synthetic Lethality with PARP inhibitors in Ovarian Cancer Drug Resist. Updat. (IF 24.3) 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
-
Solving the antibacterial resistance in Europe: The multipronged approach of the COST Action CA21145 EURESTOP Drug Resist. Updat. (IF 24.3) 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
-
Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy Drug Resist. Updat. (IF 24.3) 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
-
AI in infectious diseases: The role of datasets Drug Resist. Updat. (IF 24.3) 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
-
Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance Drug Resist. Updat. (IF 24.3) 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
-
ABCB1-dependent collateral sensitivity of multidrug-resistant colorectal cancer cells to the survivin inhibitor MX106-4C Drug Resist. Updat. (IF 24.3) 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
-
Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-04 Qingxiang Lin, Andrea Serratore, Jin Niu, Shichen Shen, Tista Roy Chaudhuri, Wen Wee Ma, Jun Qu, Eugene S. Kandel, Robert M. Straubinger
Pancreatic ductal adenocarcinoma (PDAC) is often intrinsically-resistant to standard-of-care chemotherapies such as gemcitabine. Acquired gemcitabine resistance (GemR) can arise from treatment of initially-sensitive tumors, and chemotherapy can increase tumor aggressiveness. We investigated the molecular mechanisms of chemoresistance and chemotherapy-driven tumor aggressiveness, which are understood
-
Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-01 Xueqi Ou, Yeru Tan, Jindong Xie, Jingping Yuan, Xinpei Deng, Ruonan Shao, Cailu Song, Xi Cao, Xiaoming Xie, Rongfang He, Yuehua Li, Hailin Tang
This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer. Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A
-
The role of ABCC10/MRP7 in anti-cancer drug resistance and beyond Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-29 Da-Qian Chen, Yuhao Xie, Lu-Qi Cao, Joshua S. Fleishman, Yang Chen, Tiesong Wu, Dong-Hua Yang
Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety
-
Phage-mediated colistin resistance in Acinetobacter baumannii Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-28 Massimiliano Lucidi, Francesco Imperi, Irene Artuso, Giulia Capecchi, Cinzia Spagnoli, Daniela Visaggio, Giordano Rampioni, Livia Leoni, Paolo Visca
Antimicrobial resistance is a global threat to human health, and is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant . strains has forced the revival of colistin as a last-resort drug, suddenly leading to the emergence of colistin resistance. We investigated the genetic and molecular basis of colistin resistance
-
Target-based drug design strategies to overcome resistance to antiviral agents: opportunities and challenges Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-26 Shaoqing Du, Xueping Hu, Luis Menéndez-Arias, Peng Zhan, Xinyong Liu
Viral infections have a major impact in human health. Ongoing viral transmission and escalating selective pressure have the potential to favor the emergence of vaccine- and antiviral drug-resistant viruses. Target-based approaches for the design of antiviral drugs can play a pivotal role in combating drug-resistant challenges. Drug design computational tools facilitate the discovery of novel drugs
-
Utilizing non-coding RNA-mediated regulation of ATP binding cassette (ABC) transporters to overcome multidrug resistance to cancer chemotherapy Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-20 Kenneth K.W. To, Zoufang Huang, Hang Zhang, Charles R. Ashby Jr., Liwu Fu
Multidrug resistance (MDR) is one of the primary factors that produces treatment failure in patients receiving cancer chemotherapy. MDR is a complex multifactorial phenomenon, characterized by a decrease or abrogation of the efficacy of a wide spectrum of anticancer drugs that are structurally and mechanistically distinct. The overexpression of the ATP-binding cassette (ABC) transporters, notably ABCG2
-
Polyphenol nanocomplex modulates lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-20 Zhan Zhang, Xinnan Li, Weiqiang Liu, Guanglei Chen, Jinchi Liu, Qingtian Ma, Pengjie Hou, Lu Liang, Caigang Liu
Cancer lactate metabolic reprogramming induces an elevated level of extracellular lactate and H, leading to an acidic immunosuppressive tumor microenvironment (TEM). High lactic acid level may affect the metabolic programs of various cells that comprise an antitumor immune response, therefore, restricting immune-mediated tumor destruction, and leading to therapeutic resistance and unsatisfactory prognosis
-
MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-19 Jiaqi Liang, Guoshu Bi, Yiwei Huang, Guangyin Zhao, Qihai Sui, Huan Zhang, Yunyi Bian, Jiacheng Yin, Qun Wang, Zhencong Chen, Cheng Zhan
Lung cancer is the leading cause of cancer mortality and lung adenocarcinoma (LUAD) accounts for more than half of all lung cancer cases. Tumor elimination is mostly hindered by drug resistance and the mechanisms remain to be explored in LUAD. CRISPR screens in cell and murine models and single-cell RNA sequencing were conducted, which identified MAF bZIP transcription factor F (MAFF) as a critical
-
Drug resistance mechanisms in dopamine agonist-resistant prolactin pituitary neuroendocrine tumors and exploration for new drugs Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-19 Jianhua Cheng, Weiyan Xie, Yiyuan Chen, Yingxuan Sun, Lei Gong, Hongyun Wang, Chuzhong Li, Yazhuo Zhang
The treatment of dopamine agonists (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently no viable alternative drug therapies available. This study seeks to investigate the mechanism of DA resistance in prolactinomas and identify new potentially effective drugs. To explore the mechanism of DA resistance in prolactinomas
-
Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-19 Fei Li, Henghui Zhang, Yuan Huang, Dongqing Li, Zaosong Zheng, Kunfeng Xie, Chun Cao, Qiong Wang, Xinlei Zhao, Zehai Huang, Shijun Chen, Haiyong Chen, Qin Fan, Fan Deng, Lina Hou, Xiaolin Deng, Wanlong Tan
Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that
-
Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-18 Jie Chen, Di Zhao, Lingyuan Zhang, Jing Zhang, Yuanfan Xiao, Qingnan Wu, Yan Wang, Qimin Zhan
Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis-promoting
-
Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-17 Yuna Kim, Kwan-Young Jung, Yun Hak Kim, Pan Xu, Baeki E. Kang, Yunju Jo, Navin Pandit, Jeongho Kwon, Karim Gariani, Joanna Gariani, Junguee Lee, Jef Verbeek, Seungyoon Nam, Sung-Jin Bae, Ki-Tae Ha, Hyon-Seung Yi, Minho Shong, Kyun-Hwan Kim, Doyoun Kim, Hee Jung Jung, Chang-Woo Lee, Kwang Rok Kim, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu
-
Dual specific phosphatase 4 suppresses ferroptosis and enhances sorafenib resistance in hepatocellular carcinoma Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-10 Shi-Hui Hao, Xiao-Dan Ma, Li Xu, Jing-Dun Xie, Zi-Hao Feng, Jie-Wei Chen, Ri-Xin Chen, Feng-Wei Wang, Yu-Hao Tang, Dan Xie, Mu-Yan Cai
-
Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-09 Hailin Zou, Juan Luo, Yibo Guo, Liang Deng, Leli Zeng, Yihang Pan, Peng Li
Trastuzumab resistance in HER2+ breast cancer (BC) is the major reason leading to poor prognosis of BC patients. Oncogenic gene overexpression or aberrant activation of tyrosine kinase SRC is identified to be the key modulator of trastuzumab response. However, the detailed regulatory mechanisms underlying SRC activation-associated trastuzumab resistance remain poorly understood. In the present study
-
NDRG1 overcomes resistance to immunotherapy of pancreatic ductal adenocarcinoma through inhibiting ATG9A-dependent degradation of MHC-1 Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-09 Zhiheng Zhang, Bojiao Song, Haowei Wei, Yang Liu, Wenjie Zhang, Yuhong Yang, Beicheng Sun
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is resistant to immune checkpoint blockade (ICB) therapies. Emerging evidence suggests that NDRG1 may be an important target for the development of new therapies for PDAC. Herein, we investigated the novel roles of NDRG1 and Combretastatin A-4 (CA-4) in the treatment of PDAC ICB resistance. Enrichment of MHC class I was detected by RNA
-
-
Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-04 Yuanfang Li, Baiwei Zhao, Juzheng Peng, Hailin Tang, Sicheng Wang, Sicheng Peng, Feng Ye, Junye Wang, Kai Ouyang, Jianjun Li, Manbo Cai, Yongming Chen
Drug resistance in cancer remains a major challenge in oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as a critical player in the development of drug resistance in cancer cells. This comprehensive review explores the intricate relationship between NF-κB and drug resistance in cancer. We delve into the molecular
-
The promising role of tumor-associated macrophages in the treatment of cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-03 Hongbin Wang, Xueying Wang, Xin Zhang, Wanhai Xu
Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion and metastasis, extracellular matrix remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and phagocytosis. Therefore, using macrophages for
-
Vaccine effects on COVID-19 infection with bivalent boosting by age group Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-27 Y, o, s, h, i, y, a, s, u, , T, a, k, e, f, u, j, i
This paper examines time-series vaccine effectiveness on COVID-19 infection with/without a bivalent booster dose by 6 age groups such as 18–29, 30–49, 50–64, 65–79, 80+, and all_ages respectively. CDC’s COVID data on rates of COVID-19 cases and deaths by updated (bivalent) booster status was used in this study. This result concludes that there is no difference between vaccines with or without a bivalent
-
Dynamic within-host cefiderocol heteroresistance caused by blaSHV-12 amplification in pandrug-resistant and hypervirulent Klebsiella pneumoniae sequence type 11 Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-27 Chao Liu, Juan Yi, Ming Lu, Ping Yang, Chunjing Du, Fan Jiang, Pengcheng Du, Ning Shen
Although cefiderocol (FDC) is not prescribed in China, FDC-resistant pandrug-resistant hypervirulent (PDR-hvKp) is emerging. In this study, we performed FDC susceptibility testing of clinical Kp isolates to explore the prevalence of FDC-resistant isolates and the mechanism of FDC-resistance. We retrospectively selected 151 carbapenem-resistant Kp isolates to assess FDC susceptibility. Seven isolates
-
Rewiring chaperone-mediated autophagy in cancer by a prion-like chemical inducer of proximity to counteract adaptive immune resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-25 Jin Yan, Dan Liu, Jingmei Wang, Weiming You, Wenguang Yang, Siqi Yan, Wangxiao He
Chaperone-mediated autophagy (CMA), a proteolytic system contributing to the degradation of intracellular proteins in lysosomes, is upregulated in tumors for pro-tumorigenic and pro-survival purposes. In this study, bioinformatics analysis revealed the co-occurrence of upregulated CMA and PD-L1 accumulation in metastatic melanoma with adaptive immune resistance (AIR) to anti-PD1 treatment, suggesting
-
Global spread characteristics of CTX-M-type extended-spectrum β-lactamases: A genomic epidemiology analysis Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-23 Keyi Yu, Zhenzhou Huang, Yue Xiao, He Gao, Xuemei Bai, Duochun Wang
Extended-spectrum β-lactamases (ESBLs) producing bacteria have spread worldwide and become a global public health concern. Plasmid-mediated transfer of ESBLs is an important route for resistance acquisition. We collected 1345 complete sequences of plasmids containing CTX-Ms from public database. The global transmission pattern of plasmids and evolutionary dynamics of CTX-Ms have been inferred. We applied
-
Cefiderocol: Clinical application and emergence of resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-18 Liang Wang, Jie Zhu, Liang Chen, Hong Du
Antibacterial drug resistance of gram-negative bacteria (GNB) results in high morbidity and mortality of GNB infection, seriously threaten human health globally. Developing new antibiotics has become the critical need for dealing with drug-resistant bacterial infections. Cefiderocol is an iron carrier cephalosporin that achieves drug accumulation through a unique “Trojan horse” strategy into the bacterial
-
Progress in characterizing ABC multidrug transporters in zebrafish Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-17 Joanna R. Thomas, William J.E. Frye, Robert W. Robey, Michael M. Gottesman
Zebrafish have proved to be invaluable for modeling complex physiological processes shared by all vertebrate animals. Resistance of cancers and other diseases to drug treatment can occur owing to expression of the ATP-dependent multidrug transporters ABCB1, ABCG2, and ABCC1, either because of expression of these transporters by the target cells to reduce intracellular concentrations of cytotoxic drugs
-
Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-09 Xu Lin, Qingyi Zhang, Qi Li, Jun Deng, Shuying Shen, Muhu Tang, Xianghua Ye, Cong Ji, Yuhong Yang, Yuxiao Chen, Liping Zeng, Jiangang Zhao, M.B.N. Kouwenhoven, Don Eliseo Lucero-Prisno III, Junjie Huang, Yangling Li, Bo Zhang, Jian Hu
-
TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-09 Wenxiao Jiang, Guanning Huang, Shuya Pan, Xin Chen, Ting Liu, Ziyi Yang, Tianfeng Chen, Xueqiong Zhu
-
Combating bacterial infections with host defense peptides: Shifting focus from bacteria to host immunity Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-30 Nan Gao, Jiajun Wang, Chunyang Fang, Pengfei Bai, Yu Sun, Wanpeng Wu, Anshan Shan
The increasing prevalence of multidrug-resistant bacterial infections necessitates the exploration of novel paradigms for anti-infective therapy. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have garnered extensive recognition as immunomodulatory molecules that leverage natural host mechanisms to enhance therapeutic benefits. The unique immune mechanism exhibited by certain
-
Global distribution and genomic characteristics of carbapenemase-producing Escherichia coli among humans, 2005–2023 Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-03 Yan Li, Xinran Sun, Ning Dong, Zhiqiang Wang, Ruichao Li
Carbapenem-resistant Escherichia coli (CREC) has become a major public health problem worldwide. To date, there is a limited understanding of the global distribution of CREC. In this study, we performed a comprehensive genomic analysis of 7, 731 CRECs of human origin collected from different countries worldwide between 2005 and 2023. Our results showed that these CRECs were distributed in 75 countries
-
Deciphering the genetic basis of resistome and virulome diversity among multidrug-resistant Mycoplasma hominis Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-30 Wenwen Liu, Yawen Yu, Yuting Wang, Ting Yang, Yingying Kong, Xinyou Xie, Jun Zhang
Mycoplasma hominis, a commensal bacterium that commonly inhabits the genital tract, leading to infections in both the genitourinary and extragenital regions. However, the antimicrobial resistance and pathogenic mechanisms of M. hominis isolated from extra-urogenital cystic abscess is largely unknown. This study reports the genomic epidemiological characteristics of a M. hominis isolate recovered from
-
Overexpression of ABCC1 and ABCG2 confers resistance to talazoparib, a poly (ADP-Ribose) polymerase inhibitor Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-29 Qiu-Xu Teng, Zi-Ning Lei, Jing-Quan Wang, Yuqi Yang, Zhuo-Xun Wu, Nikita Dilip Acharekar, Wei Zhang, Sabesan Yoganathan, Yihang Pan, John Wurpel, Zhe-Sheng Chen, Shuo Fang
The overexpression of ABC transporters on cancer cell membranes is one of the most common causes of multidrug resistance (MDR). This study investigates the impact of ABCC1 and ABCG2 on the resistance to talazoparib (BMN-673), a potent poly (ADP-ribose) polymerase (PARP) inhibitor, in ovarian cancer treatment. The cell viability test was used to indicate the effect of talazoparib in different cell lines
-
The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-28 Jianyou Gu, Junfeng Zhang, Renpei Xia, Xianxing Wang, Jiali Yang, Fuming Xie, Qiang Zhou, Jinghe Li, Tao Zhang, Qing Chen, Yingfang Fan, Shixiang Guo, Huaizhi Wang
Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis-
-
MYC expression and fatty acid oxidation in EGFR-TKI acquired resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-13 GuoSheng Wang, Tao Li, Yuan Wan, Qiang Li
This report expands on our previous research, highlighting a unique inverse correlation between MYC expression in tumor cells and immune cells during the development of EGFR-TKI resistance. It is observed that MYC expression and fatty acid oxidation (FAO) metabolism in tissue-resident memory (TRM) CD8 + T cells are significantly impaired. These findings offer new insights into the mechanisms of TKI
-
Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-11 Yumin Wang, Yongming Chen, Junjing Zhang, Yihui Yang, Joshua S. Fleishman, Yan Wang, Jinhua Wang, Jichao Chen, Yuanfang Li, Hongquan Wang
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
-
ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-08 Sabina Ranjit, Yao Wang, Jingwen Zhu, Satish B. Cheepala, Erin G. Schuetz, Woo Jung Cho, Beisi Xu, Camenzind G. Robinson, Gang Wu, Anjaparavanda.P. Naren, John D. Schuetz
The role of ABCC4, an ATP-binding cassette transporter, in the process of platelet formation, megakaryopoiesis, is unknown. Here, we show that ABCC4 is highly expressed in 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
-
CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress Drug Resist. Updat. (IF 24.3) Pub Date : 2023-10-29 Yuanjun Lu, Yau-Tuen Chan, Junyu Wu, Zixin Feng, Hongchao Yuan, Qiucheng Li, Tingyuan Xing, Lin Xu, Cheng Zhang, Hor-Yue Tan, Terence Kin-Wah Lee, Yibin Feng, Ning Wang
Aims 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. Methods 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
-
Promising role of protein arginine methyltransferases in overcoming anti-cancer drug resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-03 Yongxia Zhu, Tong Xia, Da-Qian Chen, Xia Xiong, Lihong Shi, Yueqi Zuo, Hongtao Xiao, Li Liu
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
-
Cisplatin-activated ERβ/DCAF8 positive feedback loop induces chemoresistance in non-small cell lung cancer via PTEN/Akt axis Drug Resist. Updat. (IF 24.3) Pub Date : 2023-10-26 Yumeng Hu, Yongjie Xu, Ting Zhang, Qianying Han, Li Li, Mingyang Liu, Ni Li, Genze Shao
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 in vitro and in vivo. Mechanically, cisplatin directly binds to
-
Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-10-22 Huize Shen, Rui Zhu, Yanyang Liu, Yangjian Hong, Jiaming Ge, Jie Xuan, Wenyuan Niu, Xuefei Yu, Jiang-Jiang Qin, Qinglin Li
-
Antibiotic failure: Beyond antimicrobial resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-10-18 Cesar de la Fuente-Nunez, Angela Cesaro, Robert E.W. Hancock
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
-
Perspectives on drug repurposing to overcome cancer multidrug resistance mediated by ABCB1 and ABCG2 Drug Resist. Updat. (IF 24.3) Pub Date : 2023-10-10 Chung-Pu Wu, Sung-Han Hsiao, Yu-Shan Wu
The overexpression of the human ATP-binding cassette (ABC) transporters in cancer cells is a common mechanism involved in developing multidrug resistance (MDR). Unfortunately, there are currently no approved drugs specifically designed to treat multidrug-resistant cancers, making MDR a significant obstacle to successful chemotherapy. Despite over two decades of research, developing transporter-specific
-
Pdr5: A master of asymmetry Drug Resist. Updat. (IF 24.3) Pub Date : 2023-10-07 John Golin, Lutz Schmitt
Pdr5 is a founding member of a large (pdr) subfamily of clinically and agriculturally significant fungal ABC transporters. The tremendous power of yeast genetics combined with biochemical and structural approaches revealed the astonishing asymmetry of this efflux pump. Asymmetry is manifested in Pdr5′s ATP-binding sites, drug binding sites, signal transformation interface, and molecular exit gate.
-
Second-site suppressor mutations reveal connection between the drug-binding pocket and nucleotide-binding domain 1 of human P-glycoprotein (ABCB1) Drug Resist. Updat. (IF 24.3) Pub Date : 2023-09-27 Megumi Murakami, Andaleeb Sajid, Sabrina Lusvarghi, Stewart R. Durell, Biebele Abel, Shahrooz Vahedi, John Golin, Suresh V. Ambudkar
Human P-glycoprotein (P-gp) or ABCB1 is overexpressed in many cancers and has been implicated in altering the bioavailability of chemotherapeutic drugs due to their efflux, resulting in the development of chemoresistance. To elucidate the mechanistic aspects and structure-function relationships of P-gp, we previously utilized a tyrosine (Y)-enriched P-gp mutant (15Y) and demonstrated that at least
-
Antibody evasion associated with the RBD significant mutations in several emerging SARS-CoV-2 variants and its subvariants Drug Resist. Updat. (IF 24.3) Pub Date : 2023-09-22 Manojit Bhattacharya, Srijan Chatterjee, Sang-Soo Lee, Kuldeep Dhama, Chiranjib Chakraborty
Since the origin of the wild strain of SARS-CoV-2, several variants have emerged, which were designated as VOC, VOI, and VUM from time to time. The Omicron variant is noted as the recent VOC. After the origin of the Omicron variant on November 2021, several subvariants of Omicron have originated subsequently, like BA.1/2, BA.2.75/2.75.2, BA.4/5, BF.7, BQ.1/1.1, XBB.1/1.5, etc. which are circulated
-
Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells Drug Resist. Updat. (IF 24.3) Pub Date : 2023-09-17 Kornélia Szebényi, András Füredi, Eszter Bajtai, Sai Nagender Sama, Agnes Csiszar, Balázs Gombos, Pál Szabó, Michael Grusch, Gergely Szakács
Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped to survive and quickly regrow, or through the acquisition of mutations during chemotherapy. Here we show that following in vitro treatment by chemotherapy, epithelial breast cancer cells adopt a transient drug tolerant phenotype characterized by cell cycle arrest, epithelial-to-mesenchymal transition
-
The definition and global epidemiology of nonmobile colistin resistance (NMCR-3) determinants in Aeromonas from 1968 to 2022 Drug Resist. Updat. (IF 24.3) Pub Date : 2023-09-07 Keyi Yu, Zhenzhou Huang, Yue Xiao, Xuemei Bai, He Gao, Duochun Wang
Polymyxins are the last line of defense in infections caused by multidrug-resistant Gram-negative bacteria. The chromosomal EptA in Aeromonas genus was defined as a nonmobile colistin resistance determinant 3 (NMCR-3). A total of 14 NMCR-3 genotypes were identified. The global prevalence of Aeromonas-borne NMCRs and MCRs indicates an increasing trend from 1968 to 2022. And an index of resistance risk
-
CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification Drug Resist. Updat. (IF 24.3) Pub Date : 2023-09-02 Yangyang Zhan, Yang Liu, Rui Yang, Qiong Chen, Fei Teng, Yueying Huang, Xin Jiang, Yueming Wang, Bin Yu, Ding Zhang, Leilei Bao, Xinli Liu, Jiwei Huang
Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy
-
Treatment Strategies and Drug Resistance Mechanisms in Adenocarcinoma of Different Organs Drug Resist. Updat. (IF 24.3) Pub Date : 2023-08-22 Peng Xing, Shuo Wang, Yu Cao, Bo Liu, Feifei Zheng, Wei Guo, Junhao Huang, Zimo Zhao, Ziyi Yang, Xingda Lin, Liang Sang, Zhe Liu
Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review
-
Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2023-08-21 Pradhapsingh Bharathiraja, Priya Yadav, Andaleeb Sajid, Suresh V. Ambudkar, N. Rajendra Prasad
ATP-binding cassette (ABC) transporters such as ABCB1, ABCG2, and ABCC1 are the major players in drug efflux-mediated multidrug resistance (MDR), which severely affects the efficacy of chemotherapy. Several synthetic compounds block the drug transport by ABC transporters; however, they exhibit a narrow therapeutic window, and produce side effects in non-target normal tissues. Conversely, the downregulation
-
Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2023-08-21 Wei Zhang, Yibao Fan, Jinze Zhang, Dan Shi, Jiahui Yuan, Milad Ashrafizadeh, Wei Li, Man Hu, A.M. Abd El-Aty, Ahmet Hacimuftuoglu, Michael Linnebacher, Yongxian Cheng, Weiguang Li, Shuo Fang, Peng Gong, Xianbin Zhang
Aims Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle
-
H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase Drug Resist. Updat. (IF 24.3) Pub Date : 2023-08-10 Dinoop Ravindran Menon, Heinz Hammerlindl, Gregory Gimenez, Sabrina Hammerlindl, Elmar Zuegner, Joachim Torrano, Natalie Bordag, Abdullah Al Emran, Maybelline Giam, Simon Denil, Norman Pavelka, Aik-Choon Tan, Richard A. Sturm, Nikolas K. Haass, Giulia Rancati, Meenhard Herlyn, Christoph Magnes, Michael R. Eccles, Mayumi Fujita, Helmut Schaider
Aims Drivers of the drug tolerant proliferative persister (DTPP) state have not been well investigated. Histone H3 lysine-4 trimethylation (H3K4me3), an active histone mark, might enable slow cycling drug tolerant persisters (DTP) to regain proliferative capacity. This study aimed to determine H3K4me3 transcriptionally active sites identifying a key regulator of DTPPs. Methods Deploying a model of
-
Structure, function, and inhibition of catalytically asymmetric ABC transporters: Lessons from the PDR subfamily Drug Resist. Updat. (IF 24.3) Pub Date : 2023-08-05 Atanu Banerjee, Jorgaq Pata, Vincent Chaptal, Ahcène Boumendjel, Pierre Falson, Rajendra Prasad
ATP-binding cassette (ABC) superfamily comprises a large group of ubiquitous transmembrane proteins that play a crucial role in transporting a diverse spectrum of substrates across cellular membranes. They participate in a wide array of physiological and pathological processes including nutrient uptake, antigen presentation, toxin elimination, and drug resistance in cancer and microbial cells. ABC
-
Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment Drug Resist. Updat. (IF 24.3) Pub Date : 2023-07-31 Daniele Focosi, Scott McConnell, David J. Sullivan, Arturo Casadevall
The mutation rate of the Omicron sublineage has led to baseline resistance against all previously authorized anti-Spike monoclonal antibodies (mAbs). Nevertheless, in case more antiviral mAbs will be authorized in the future, it is relevant to understand how frequently treatment-emergent resistance has emerged so far, under different combinations and in different patient subgroups. We report the results