癌症耐药(英文)最新文献

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Recent advances in access to overcome cancer drug resistance by nanocarrier drug delivery system. 纳米载体给药系统攻克癌症耐药途径的最新进展。
癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2023.16
Xiangyu Sun, Ping Zhao, Jierou Lin, Kun Chen, Jianliang Shen
{"title":"Recent advances in access to overcome cancer drug resistance by nanocarrier drug delivery system.","authors":"Xiangyu Sun,&nbsp;Ping Zhao,&nbsp;Jierou Lin,&nbsp;Kun Chen,&nbsp;Jianliang Shen","doi":"10.20517/cdr.2023.16","DOIUrl":"https://doi.org/10.20517/cdr.2023.16","url":null,"abstract":"<p><p>Cancer is currently one of the most intractable diseases causing human death. Although the prognosis of tumor patients has been improved to a certain extent through various modern treatment methods, multidrug resistance (MDR) of tumor cells is still a major problem leading to clinical treatment failure. Chemotherapy resistance refers to the resistance of tumor cells and/or tissues to a drug, usually inherent or developed during treatment. Therefore, an urgent need to research the ideal drug delivery system to overcome the shortcoming of traditional chemotherapy. The rapid development of nanotechnology has brought us new enlightenments to solve this problem. The novel nanocarrier provides a considerably effective treatment to overcome the limitations of chemotherapy or other drugs resulting from systemic side effects such as resistance, high toxicity, lack of targeting, and off-target. Herein, we introduce several tumor MDR mechanisms and discuss novel nanoparticle technology applied to surmount cancer drug resistance. Nanomaterials contain liposomes, polymer conjugates, micelles, dendrimers, carbon-based, metal nanoparticles, and nucleotides which can be used to deliver chemotherapeutic drugs, photosensitizers, and small interfering RNA (siRNA). This review aims to elucidate the advantages of nanomedicine in overcoming cancer drug resistance and discuss the latest developments.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 2","pages":"390-415"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors. 肾癌耐药的机制和临床意义:免疫检查点抑制剂的叙述性回顾。
癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2023.02
Sunil Samnani, Faraz Sachedina, Mehul Gupta, Edward Guo, Vishal Navani
{"title":"Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors.","authors":"Sunil Samnani,&nbsp;Faraz Sachedina,&nbsp;Mehul Gupta,&nbsp;Edward Guo,&nbsp;Vishal Navani","doi":"10.20517/cdr.2023.02","DOIUrl":"https://doi.org/10.20517/cdr.2023.02","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. The prognosis for patients with ccRCC has improved over recent years with the use of combination therapies with an anti-programmed death-1 (PD-1) backbone. This has enhanced the quality of life and life expectancy of patients with this disease. Unfortunately, not all patients benefit; eventually, most patients will develop resistance to therapy and progress. Recent molecular, biochemical, and immunological research has extensively researched anti-angiogenic and immune-based treatment resistance mechanisms. This analysis offers an overview of the principles underpinning the resistance pathways related to immune checkpoint inhibitors (ICIs). Additionally, novel approaches to overcome resistance that may be considered for the trial context are discussed.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 2","pages":"416-429"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Concomitant medications and circulating tumor cells: friends or foes? 伴随用药与循环肿瘤细胞:是友是敌?
癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2022.68
Serena Di Cosimo, Vera Cappelletti
{"title":"Concomitant medications and circulating tumor cells: friends or foes?","authors":"Serena Di Cosimo,&nbsp;Vera Cappelletti","doi":"10.20517/cdr.2022.68","DOIUrl":"https://doi.org/10.20517/cdr.2022.68","url":null,"abstract":"<p><p>The use of concomitant medications by patients with cancer is observed almost globally; however, little attention has been paid to this topic in the medical literature. Most clinical studies do not describe the type and duration of drugs used at the time of inclusion and during treatment or how these drugs may affect the experimental and/or standard therapy. Even less information has been published on the potential interaction between concomitant medications and tumor biomarkers. However, we do know that concomitant drugs can complicate cancer clinical trials and biomarker development, thus contributing to their interaction, leading to side effects, and resulting in suboptimal adherence to anticancer treatment. On the basis of these premises and moving from the study by Jurisova <i>et al.</i>, which reported the effect of commonly used drugs on the prognosis of women with breast cancer and the detection of circulating tumor cells (CTCs), we comment on the role of CTCs as an emerging diagnostic and prognostic tool for breast cancer. We also report the known and hypothesized mechanisms of CTC interplay with other tumor and blood components, possibly modulated by widespread drugs, including over-the-counter compounds, and discuss the possible implications of commonly used concomitant medications on CTC detection and clearance. After considering all these points, it is conceivable that concomitant drugs are not necessarily a problem, but on the contrary, their virtuous mechanisms can be exploited to reduce tumor spread and enhance the effect of anticancer therapies.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 1","pages":"30-34"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9310602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nano-TRAIL: a promising path to cancer therapy. 纳米trail:一种有前途的癌症治疗途径。
癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2022.82
Siri Chandana Gampa, Sireesha V Garimella, SanthiLatha Pandrangi
{"title":"Nano-TRAIL: a promising path to cancer therapy.","authors":"Siri Chandana Gampa,&nbsp;Sireesha V Garimella,&nbsp;SanthiLatha Pandrangi","doi":"10.20517/cdr.2022.82","DOIUrl":"https://doi.org/10.20517/cdr.2022.82","url":null,"abstract":"<p><p>Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, also called apo-2 ligand (TRAIL/Apo-2L), is a cytokine that triggers apoptosis by binding to TRAIL-R1 (DR4) and TRAIL-R2 (DR5) death receptors. Apoptosis occurs through either the extrinsic or intrinsic pathway. The administration of recombinant human TRAIL (rhTRAIL) or TRAIL-receptor (TRAIL-R) agonists promotes apoptosis preferentially in cancerous cells over normal cells <i>in vitro</i>; this phenomenon has also been observed in clinical studies. The limited efficacy of rhTRAIL in clinical trials could be attributed to drug resistance, short half-life, targeted delivery issues, and off-target toxicities. Nanoparticles are excellent drug and gene delivery systems characterized by improved permeability and retention, increased stability and biocompatibility, and precision targeting. In this review, we discuss resistance mechanisms to TRAIL and methods to overcome TRAIL resistance by using nanoparticle-based formulations developed for the delivery of TRAIL peptides, TRAIL-R agonists, and TRAIL genes to cancer cells. We also discuss combinatorial approaches of chemotherapeutic drugs with TRAIL. These studies demonstrate TRAIL's potential as an anticancer agent.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 1","pages":"78-102"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations: acquired resistance mechanisms and strategies to overcome them. 抗血管生成单克隆抗体联合表皮生长因子受体-TKIs在治疗表皮生长因子受体活化突变的晚期非小细胞肺癌中的作用:获得性耐药机制及克服策略。
IF 4.6
癌症耐药(英文) Pub Date : 2022-11-02 eCollection Date: 2022-01-01 DOI: 10.20517/cdr.2022.77
Danilo Rocco, Luigi Della Gravara, Giovanni Palazzolo, Cesare Gridelli
{"title":"The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations: acquired resistance mechanisms and strategies to overcome them.","authors":"Danilo Rocco, Luigi Della Gravara, Giovanni Palazzolo, Cesare Gridelli","doi":"10.20517/cdr.2022.77","DOIUrl":"10.20517/cdr.2022.77","url":null,"abstract":"<p><p>As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for the first-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab and erlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due to several different acquired resistance mechanisms, mainly represented by T790M substitutions and MET amplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment, MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a role for MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatment algorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also represent another useful addition.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"5 4","pages":"1016-1024"},"PeriodicalIF":4.6,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10519778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanisms of neratinib resistance in HER2-mutant metastatic breast cancer. HER2突变转移性乳腺癌的奈瑞替尼耐药机制
IF 4.6
癌症耐药(英文) Pub Date : 2022-09-01 eCollection Date: 2022-01-01 DOI: 10.20517/cdr.2022.48
Lisa D Eli, Shyam M Kavuri
{"title":"Mechanisms of neratinib resistance in <i>HER2</i>-mutant metastatic breast cancer.","authors":"Lisa D Eli, Shyam M Kavuri","doi":"10.20517/cdr.2022.48","DOIUrl":"10.20517/cdr.2022.48","url":null,"abstract":"<p><p>Human epidermal growth factor receptor 2 (HER2) is a major drug target and clinical biomarker in breast cancer treatment. Targeting <i>HER2</i> gene amplification is one of the greatest successes in oncology, resulting in the use of a wide array of HER2-directed agents in the clinic. The discovery of <i>HER2</i>-activating mutations as novel therapeutic targets in breast and other cancers marked a significant advance in the field, which led to the metastatic breast and other solid tumor trials MutHER (NCT01670877), SUMMIT (NCT01953926), and one arm of plasmaMATCH (NCT03182634). These trials reported initial clinical benefit followed by eventual relapse ascribed to either primary or acquired resistance. These resistance mechanisms are mediated by additional secondary genomic alterations within <i>HER2</i> itself and via hyperactivation of oncogenic signaling within the downstream signaling axis.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"5 4","pages":"873-881"},"PeriodicalIF":4.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces. 癌症干细胞的抗药性和抗凋亡性:一块块拼图。
IF 4.6
癌症耐药(英文) Pub Date : 2022-08-02 eCollection Date: 2022-01-01 DOI: 10.20517/cdr.2022.20
Ahmad R Safa
{"title":"Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces.","authors":"Ahmad R Safa","doi":"10.20517/cdr.2022.20","DOIUrl":"10.20517/cdr.2022.20","url":null,"abstract":"<p><p>Resistance to anticancer agents and apoptosis results in cancer relapse and is associated with cancer mortality. Substantial data have provided convincing evidence establishing that human cancers emerge from cancer stem cells (CSCs), which display self-renewal and are resistant to anticancer drugs, radiation, and apoptosis, and express enhanced epithelial to mesenchymal progression. CSCs represent a heterogeneous tumor cell population and lack specific cellular targets, which makes it a great challenge to target and eradicate them. Similarly, their close relationship with the tumor microenvironment creates greater complexity in developing novel treatment strategies targeting CSCs. Several mechanisms participate in the drug and apoptosis resistance phenotype in CSCs in various cancers. These include enhanced expression of ATP-binding cassette membrane transporters, activation of various cytoprotective and survival signaling pathways, dysregulation of stemness signaling pathways, aberrant DNA repair mechanisms, increased quiescence, autophagy, increased immune evasion, deficiency of mitochondrial-mediated apoptosis, upregulation of anti-apoptotic proteins including c-FLIP [cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein], Bcl-2 family members, inhibitors of apoptosis proteins, and PI3K/AKT signaling. Studying such mechanisms not only provides mechanistic insights into these cells that are unresponsive to drugs, but may lead to the development of targeted and effective therapeutics to eradicate CSCs. Several studies have identified promising strategies to target CSCs. These emerging strategies may help target CSC-associated drug resistance and metastasis in clinical settings. This article will review the CSCs drug and apoptosis resistance mechanisms and how to target CSCs.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"5 4","pages":"850-872"},"PeriodicalIF":4.6,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combating CHK1 resistance in triple negative breast cancer: EGFR inhibition as potential combinational therapy. 对抗三阴性乳腺癌的CHK1耐药:EGFR抑制作为潜在的联合治疗
IF 4.6
癌症耐药(英文) Pub Date : 2022-03-08 eCollection Date: 2022-01-01 DOI: 10.20517/cdr.2021.128
Casey D Stefanski, Jenifer R Prosperi
{"title":"Combating CHK1 resistance in triple negative breast cancer: EGFR inhibition as potential combinational therapy.","authors":"Casey D Stefanski, Jenifer R Prosperi","doi":"10.20517/cdr.2021.128","DOIUrl":"10.20517/cdr.2021.128","url":null,"abstract":"<p><p>Triple negative breast cancer (TNBC) is marked by a lack of expression of the Estrogen Receptor, Progesterone Receptor, and human epidermal growth factor receptor 2. Therefore, targeted therapies are being investigated based on the expression profiles of tumors. Due to the potential for acquired and intrinsic resistance, there is a need for combination therapy to overcome resistance. In the article by Lee et al., the authors identify that, while prexasertib (a CHK1 inhibitor) lacks efficacy alone, combination with an EGFR inhibitor provides synergistic anti-tumor effects. Advances in targeted therapy for TNBC will benefit the clinical landscape for this disease, with this study initiating a new avenue of investigation.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"5 1","pages":"229-232"},"PeriodicalIF":4.6,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44833354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug resistance and minimal residual disease in multiple myeloma. 多发性骨髓瘤的耐药性和微小残留病
IF 4.6
癌症耐药(英文) Pub Date : 2022-02-16 eCollection Date: 2022-01-01 DOI: 10.20517/cdr.2021.116
Alessandro Gozzetti, Sara Ciofini, Anna Sicuranza, Paola Pacelli, Donatella Raspadori, Emanuele Cencini, Dania Tocci, Monica Bocchia
{"title":"Drug resistance and minimal residual disease in multiple myeloma.","authors":"Alessandro Gozzetti, Sara Ciofini, Anna Sicuranza, Paola Pacelli, Donatella Raspadori, Emanuele Cencini, Dania Tocci, Monica Bocchia","doi":"10.20517/cdr.2021.116","DOIUrl":"10.20517/cdr.2021.116","url":null,"abstract":"<p><p>Great progress has been made in improving survival in multiple myeloma (MM) patients over the last 30 years. New drugs have been introduced and complete responses are frequently seen. However, the majority of MM patients do experience a relapse at a variable time after treatment, and ultimately the disease becomes drug-resistant following therapies. Recently, minimal residual disease (MRD) detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response. MRD can be considered as a surrogate for both progression-free and overall survival. In this perspective, the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals. The present review gives an overview of drug resistance in MM, i.e., mutation of β5 subunit of the proteasome; upregulation of pumps of efflux; heat shock protein induction for proteasome inhibitors; downregulation of <i>CRBN</i> expression; deregulation of <i>IRF4</i> expression; mutation of <i>CRBN</i>, <i>IKZF1</i>, and <i>IKZF3</i> for immunomodulatory drugs and decreased target expression; complement protein increase; sBCMA increase; and BCMA down expression for monoclonal antibodies. Multicolor flow cytometry, or next-generation flow, and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10<sup>-5</sup>. Sustained MRD negativity is related to prolonged survival, and it is evaluated in all recent clinical trials as a surrogate of drug efficacy.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"5 1","pages":"171-183"},"PeriodicalIF":4.6,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44851889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of extracellular vesicles secretion in paclitaxel resistance of prostate cancer cells. 细胞外囊泡分泌在前列腺癌细胞紫杉醇耐药中的作用。
癌症耐药(英文) Pub Date : 2022-01-01 DOI: 10.20517/cdr.2022.26
Ashish Kumar, Pawan Kumar, Mitu Sharma, Susy Kim, Sangeeta Singh, Steven J Kridel, Gagan Deep
{"title":"Role of extracellular vesicles secretion in paclitaxel resistance of prostate cancer cells.","authors":"Ashish Kumar,&nbsp;Pawan Kumar,&nbsp;Mitu Sharma,&nbsp;Susy Kim,&nbsp;Sangeeta Singh,&nbsp;Steven J Kridel,&nbsp;Gagan Deep","doi":"10.20517/cdr.2022.26","DOIUrl":"https://doi.org/10.20517/cdr.2022.26","url":null,"abstract":"<p><p><b>Aim:</b> The development of chemotherapy resistance is the major obstacle in the treatment of advanced prostate cancer (PCa). Extracellular vesicles (EVs) secretion plays a significant role among different mechanisms contributing to chemoresistance. Hence, inhibition of EVs release may increase the efficacy of chemotherapeutic drugs against PCa. <b>Methods:</b> Paclitaxel (PTX) resistant PCa cells (PC3-R and DU145-R) were treated with GW4869, a known exosome biogenesis inhibitor. EVs were isolated from the conditioned media by ExoQuick-based precipitation method and characterized for concentration and size distribution by nanoparticle tracking analysis. The effect of GW4869 treatment on the survival and growth of PCa cells was assessed by MTT, and colony formation assays <i>in vitro</i>, and ectopic PC3-R xenografts in male athymic nude mice <i>in vivo</i>. The effect of other EV biogenesis inhibitors, imipramine and dimethyl amiloride (DMA), treatment was also analyzed on the survival of PC3-R cells. <b>Results:</b> GW4869 (10-20 µM) treatment of PTX resistant PCa cells significantly reduced the release of small EVs (50-100 nm size range) while increasing the release of larger EVs (> 150 nm in size), and inhibited their clonogenicity. Moreover, GW4869 (5-20 µM) treatment (24-72h) significantly inhibited the survival of PC3-R cells in a dose-dependent manner. We observed a similar growth inhibition with both imipramine (5-20 µg/mL) and DMA (5-20 µg/mL) treatment in PC3-R cells. Furthermore, GW4869 treatment (IP) in mice bearing PC3-R xenografts significantly reduced the tumor weight (65% reduction, <i>P</i> = 0.017) compared to the vehicle-treated control mice without causing any noticeable toxicity. <b>Conclusion:</b> Inhibiting the release of EVs could sensitize the resistant PCa cells to chemotherapy.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"5 3","pages":"612-624"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9102474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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