癌症耐药(英文)最新文献_第9页

Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance. 癌症相关成纤维细胞的异型信号形成了癌细胞的抗药性。

IF 4.6

癌症耐药(英文) Pub Date : 2023-03-27 eCollection Date: 2023-01-01 DOI: 10.20517/cdr.2022.72

Ramesh Butti, Ashwini Khaladkar, Priya Bhardwaj, Gopinath Prakasam

{"title":"Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance.","authors":"Ramesh Butti, Ashwini Khaladkar, Priya Bhardwaj, Gopinath Prakasam","doi":"10.20517/cdr.2022.72","DOIUrl":"10.20517/cdr.2022.72","url":null,"abstract":"The context-dependent reciprocal interaction between the cancer cells and surrounding fibroblasts is imperative for regulating malignant potential, metabolic reprogramming, immunosuppression, and ECM deposition. However, recent evidence also suggests that cancer-associated fibroblasts induce chemoresistance in cancer cells to various anticancer regimens. Because of the protumorigenic function of cancer-associated fibroblasts, these stromal cell types have emerged as fascinating therapeutic targets for cancer. However, this notion was recently challenged by studies that targeted cancer-associated fibroblasts and highlighted the underlying heterogeneity by identifying a subset of these cells with tumor-restricting functions. Hence, it is imperative to understand the heterogeneity and heterotypic signaling of cancer-associated fibroblasts to target tumor-promoting signaling processes by sparing tumor-restricting ones. In this review, we discuss the heterogeneity and heterotypic signaling of cancer-associated fibroblasts in shaping drug resistance and also list the cancer-associated fibroblast-targeting therapeutics.","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 1","pages":"182-204"},"PeriodicalIF":4.6,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9310601","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

Targeting regulated cell death pathways in acute myeloid leukemia. 以急性髓性白血病中受调控的细胞死亡途径为靶点。

癌症耐药(英文) Pub Date : 2023-03-15 eCollection Date: 2023-01-01 DOI: 10.20517/cdr.2022.108

Sylvain Garciaz, Thomas Miller, Yves Collette, Norbert Vey

引用次数: 0

New perspectives on epigenetic modifications and PARP inhibitor resistance in HR-deficient cancers. hr缺陷癌的表观遗传修饰和PARP抑制剂耐药的新观点。

IF 4.6

癌症耐药(英文) Pub Date : 2023-01-04 eCollection Date: 2023-01-01 DOI: 10.20517/cdr.2022.73

Rachel Bayley, Ellie Sweatman, Martin R Higgs

引用次数: 0

Cancer stem cells in drug resistance: an introduction to the e-book covering the special issue on the "Cancer Stem Cells and Drug Resistance". 癌症干细胞的耐药性:介绍电子书覆盖的特刊“癌症干细胞和耐药性”。

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2023.23

Balázs Sarkadi

引用次数: 0

How acute myeloid leukemia (AML) escapes from FMS-related tyrosine kinase 3 (FLT3) inhibitors? Still an overrated complication? 急性髓性白血病(AML)如何从fms相关酪氨酸激酶3 (FLT3)抑制剂中逃脱?还是一个被高估的并发症?

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2022.130

Salvatore Perrone, Tiziana Ottone, Nadezda Zhdanovskaya, Matteo Molica

{"title":"How acute myeloid leukemia (AML) escapes from FMS-related tyrosine kinase 3 (FLT3) inhibitors? Still an overrated complication?","authors":"Salvatore Perrone, Tiziana Ottone, Nadezda Zhdanovskaya, Matteo Molica","doi":"10.20517/cdr.2022.130","DOIUrl":"https://doi.org/10.20517/cdr.2022.130","url":null,"abstract":"FMS-related tyrosine kinase 3 (FLT3) mutations, present in about 25%-30% of acute myeloid leukemia (AML) patients, constitute one of the most frequently detected mutations in these patients. The binding of FLT3L to FLT3 activates the phosphatidylinositol 3-kinase (PI3K) and RAS pathways, producing increased cell proliferation and the inhibition of apoptosis. Two types of FLT3 mutations exist: FLT3-ITD and FLT3-TKD (point mutations in D835 and I836 or deletion of codon I836). A class of drugs, tyrosine-kinase inhibitors (TKI), targeting mutated FLT3, is already available with 1st and 2nd generation molecules, but only midostaurin and gilteritinib are currently approved. However, the emergence of resistance or the selection of clones not responding to FLT3 inhibitors has become an important clinical dilemma, as the duration of clinical responses is generally limited to a few months. This review analyzes the insights into mechanisms of resistance to TKI and poses a particular view on the clinical relevance of this phenomenon. Has resistance been overlooked? Indeed, FLT3 inhibitors have significantly contributed to reducing the negative impact of FLT3 mutations on the prognosis of AML patients who are no longer considered at high risk by the European LeukemiaNet (ELN) 2022. Finally, several ongoing efforts to overcome resistance to FLT3-inhibitors will be presented: new generation FLT3 inhibitors in monotherapy or combined with standard chemotherapy, hypomethylating drugs, or IDH1/2 inhibitors, Bcl2 inhibitors; novel anti-human FLT3 monoclonal antibodies (e.g., FLT3/CD3 bispecific antibodies); FLT3-CAR T-cells; CDK4/6 kinase inhibitor (e.g., palbociclib).","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 2","pages":"223-238"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9826410","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: 2

Importance of ROS1 gene fusions in non-small cell lung cancer. ROS1基因融合在非小细胞肺癌中的重要性。

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2022.105

Meri Muminovic, Carlos Rodrigo Carracedo Uribe, Andres Alvarez-Pinzon, Khine Shan, Luis E Raez

{"title":"Importance of ROS1 gene fusions in non-small cell lung cancer.","authors":"Meri Muminovic, Carlos Rodrigo Carracedo Uribe, Andres Alvarez-Pinzon, Khine Shan, Luis E Raez","doi":"10.20517/cdr.2022.105","DOIUrl":"https://doi.org/10.20517/cdr.2022.105","url":null,"abstract":"Targeted therapy has become one of the standards of care for advanced lung cancer. More than 10 genetic aberrations have been discovered that are actionable and several tyrosine kinase inhibitors (TKIs) have been approved to target each of them. Among several genetic aberrations that are actionable in non-small cell lung cancer (NSCLC), ROS1 translocations also known as gene fusion proteins, are found in only 1%-2% of the patient population. ROS1 mutations can usually be detected using a combination of techniques such as immunohistochemistry (IHC), Fluorescence in-situ testing (FISH), polymerase chain reaction (PCR), and next-generation sequencing (NGS). However, RNA NGS and ctDNA NGS (liquid biopsies) also contribute to the diagnosis. There are currently numerous FDA-approved agents for these tumors, including crizotinib and entrectinib; however, there is in-vitro sensitivity data and clinical data documenting responses to ceritinib and lorlatinib. Clinical responses and survival rates with these agents are frequently among the best compared to other TKIs with genetic aberrations; however, intrinsic or extrinsic mechanisms of resistance may develop, necessitating research for alternative treatment modalities. To combat the mechanisms of resistance, novel agents such as repotrectenib, cabozantinib, talotrectinib, and others are being developed. In this article, we examine the literature pertaining to patients with ROS1 tumors, including epidemiology, clinical outcomes, resistance mechanisms, and treatment options.","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 2","pages":"332-344"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9826411","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: 1

miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression (WIP1) in Childhood Acute Lymphoblastic Leukemia. miR-16-5p通过靶向儿童急性淋巴细胞白血病中PPM1D表达(WIP1)增强对RG7388的敏感性。

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2022.113

Maryam Zanjirband, Soheila Rahgozar, Narges Aberuyi

{"title":"miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression (WIP1) in Childhood Acute Lymphoblastic Leukemia.","authors":"Maryam Zanjirband, Soheila Rahgozar, Narges Aberuyi","doi":"10.20517/cdr.2022.113","DOIUrl":"https://doi.org/10.20517/cdr.2022.113","url":null,"abstract":"Aim: Given the encouraging results of the p53-Mdm2 inhibitor RG7388 in clinical trials and the vital function of miR-16-5p in suppressing cell proliferation, the aim of the present study was to investigate the combined impact of RG7388 and miR-16-5p overexpression on the childhood acute lymphoblastic leukemia (chALL). Methods: miRTarBase and miRDB, along with KEGG and STRING databases, were used to predict miR-16-5p target genes and explore protein-protein interaction networks, respectively. B- and T-lymphoblastic cell lines, in addition to patient primary cells, were treated with RG7388. Ectopic overexpression of miR-16-5p in Nalm6 cell line was induced through cell electroporation and transfection of microRNA mimics was confirmed by qRT-PCR. Cell viability was evaluated using the MTT assay. Western blot analyses were performed to evaluate the effects of RG7388 and miR-16-5p upregulation on the protein levels of p53 and its downstream target genes in chALL cells. Paired sample t-test was employed for statistical analyses. Results: MTT assay showed RG7388-induced cytotoxicity in wild-type p53 Nalm6 cell line and p53 functional patient primary cells. However, CCRF-CEM and p53 non-functional leukemic cells indicated drug resistance. Western blot analyses validated the bioinformatics results, confirming the downregulation of WIP1, p53 stabilization, as well as overexpression of p21WAF1 and Mdm2 proteins in Nalm6 cells transfected with miR-16-5p. Moreover, enhanced sensitivity to RG7388 was observed in the transfected cells. Conclusion: This is the first study indicating the mechanistic importance of miR-16-5p overexpression in chALL and its inhibitory role in leukemia treatment when combined with the p53-Mdm2 antagonist, RG7388. These findings might be useful for researchers and clinicians to pave the way for better management of chALL.","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 2","pages":"242-256"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828958","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: 1

Multimodal 4-arylchromene derivatives with microtubule-destabilizing, anti-angiogenic, and MYB-inhibitory activities. 具有微管不稳定、抗血管生成和myb抑制活性的多模态4-芳基铬衍生物。

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2022.90

Leonhard H F Köhler, Sebastian Reich, Maria Yusenko, Karl-Heinz Klempnauer, Gerrit Begemann, Rainer Schobert, Bernhard Biersack

{"title":"Multimodal 4-arylchromene derivatives with microtubule-destabilizing, anti-angiogenic, and MYB-inhibitory activities.","authors":"Leonhard H F Köhler, Sebastian Reich, Maria Yusenko, Karl-Heinz Klempnauer, Gerrit Begemann, Rainer Schobert, Bernhard Biersack","doi":"10.20517/cdr.2022.90","DOIUrl":"https://doi.org/10.20517/cdr.2022.90","url":null,"abstract":"Aim: Efficient and readily available anticancer drugs are sought as treatment options. For this reason, chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic properties. Methods: 2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds (2A-R) were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol, various aryl aldehydes, and malononitrile. We performed assays to study the inhibition of tumor cell growth [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromid (MTT) assay], effects on microtubules (immunofluorescence), cell cycle (flow-activated cell sorting analysis), angiogenesis (zebrafish model), and MYB activity (luciferase reporter assay). Fluorescence microscopy was applied for localization studies via copper-catalyzed azide-alkyne click reaction of an alkyne-tagged drug derivative. Results: Compounds 2A-C and 2F exhibited robust antiproliferative activities against several human cancer cell lines (50% inhibitory concentrations in the low nanomolar range) and showed potent MYB inhibition. The alkyne derivative 3 was localized in the cytoplasm after only 10 min of incubation. Substantial microtubule disruption and G2/M cell-cycle arrest were observed, where compound 2F stood out as a promising microtubule-disrupting agent. The study of anti-angiogenic properties showed that 2A was the only candidate with a high potential to inhibit blood vessel formation in vivo. Conclusion: The close interplay of various mechanisms, including cell-cycle arrest, MYB inhibition, and anti-angiogenic activity, led to identifying promising multimodal anticancer drug candidates.","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 1","pages":"59-77"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317813","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: 1

Fungal mycobiome-mediated immune response: a non-negligible promoter in pancreatic oncogenesis and chemoresistance. 真菌菌群介导的免疫反应:胰腺肿瘤发生和化疗耐药的不可忽视的启动子。

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2023.06

Yaling Jiang, Valentina Donati, Godefridus J Peters, Elisa Giovannetti, Dong Mei Deng

引用次数: 0

Interaction of pregnane X receptor with hypoxia-inducible factor-1 regulates chemoresistance of prostate cancer cells. 孕激素X受体与缺氧诱导因子-1的相互作用调控前列腺癌细胞的化疗耐药。

癌症耐药(英文) Pub Date : 2023-01-01 DOI: 10.20517/cdr.2023.14

Jiuhui Wang, Daotai Nie

{"title":"Interaction of pregnane X receptor with hypoxia-inducible factor-1 regulates chemoresistance of prostate cancer cells.","authors":"Jiuhui Wang, Daotai Nie","doi":"10.20517/cdr.2023.14","DOIUrl":"https://doi.org/10.20517/cdr.2023.14","url":null,"abstract":"Aim: The nuclear pregnane X receptor (PXR) is a pivotal regulator of steroid and xenobiotics metabolism and plays an important role in shaping tumor cell responses to chemotherapy. Hypoxia within tumor tissue has multifaceted effects, including multiple drug resistance. The goal of this study was to determine whether PXR contributes to hypoxia-induced drug resistance. Methods: Metastatic prostate cancer cells were used to study the interaction of PXR and hypoxia-inducible factor-1 (HIF-1 in drug resistance associated with hypoxia. The activities of PXR and HIF-1 were determined by assays for its reporter gene or target gene expression. Co-immunoprecipitation (Co-IP) was used to determine the interaction of PXR and HIF-1. Ablation or inhibition of PXR or HIF-1 was used to determine their roles in hypoxia-induced chemoresistance. Results: PXR was activated by hypoxia, leading to increased expression of multidrug resistance protein 1 (MDR1). Inhibition of PXR by pharmacological compounds or depletion by shRNAs reduced the hypoxic induction of MDR1 and sensitized prostate cancer cells to chemotherapy under hypoxia. HIF-1 was required for PXR activation under hypoxia. Co-immunoprecipitation results showed that HIF-1 and PXR could physically interact with each other, leading to crosstalk between these two transcription factors. Conclusion: PXR contributes to hypoxia-induced drug resistance in prostate cancer cells through its interaction with HIF-1.","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"6 2","pages":"378-389"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828961","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