scholarly journals A novel chemical, STF-083010, reverses tamoxifen-related drug resistance in breast cancer by inhibiting IRE1/XBP1

Oncotarget ◽  
2015 ◽  
Vol 6 (38) ◽  
pp. 40692-40703 ◽  
Author(s):  
Jie Ming ◽  
Shengnan Ruan ◽  
Mengyi Wang ◽  
Dan Ye ◽  
Ningning Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Related Drug

miRNAs as modulators of cholesterol in breast cancer stem cells: an approach to overcome drug resistance in cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Bernice Monchusi ◽  
Mandeep Kaur
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Disease Free Survival ◽  
Cancer Drug ◽  
Tumour Mass ◽  
Breast Cancer Patients ◽  
Cancer Drug Resistance ◽  
Related Drug

: It has been postulated that a small number of cancer stem cells (CSCs) buried in tumour mass drive cancer growth and impart cancer drug resistance. However, their eradication has not been achieved so far as the mechanistic understanding around CSCs’ role in cancer development and growth is limited. The cholesterol accumulation and efflux processes have been shown to play an important role in maintaining cell’s integrity and its sensitivity towards drugs, as altered cholesterol pathways contribute to cancer drug resistance. Emerging evidences have indicated miRNAs as regulators of CSCs, and also as regulators of cholesterol pathways in cancer cells, but a link between the two has not been fully established so far. In this review, we have collated key signalling pathways, and published evidences emphasising the involvement of miRNAs and cholesterol in CSCs related drug resistance. Additionally, we have used bioinformatics analysis to identify miRNAs that may modulate cholesterol pathways in CSCs at molecular level to contribute to cancer drug resistance. Our results that two miRNAs (hsa-miR-34a-5p and hsa-miR-373-3p) interact, and bind to two known Breast CSC markers (CD44 and CD24), and mediate expression of several cholesterol-related genes (INSIG2, APOL2, CYP51A1, HDLB, and DHCR7). Furthermore, survival analysis of the breast cancer patients’ gene expression data revealed that higher expression of these genes is associated with poor disease free survival. We therefore propose that targeting these two miRNAs could possibly provide a way to alter cell’s response to drugs via modulating cholesterol pathway in CSCs.

scholarly journals The Breast Cancer Stem Cells Traits and Drug Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Qinghui Zheng ◽  
Mengdi Zhang ◽  
Fangfang Zhou ◽  
Long Zhang ◽  
Xuli Meng
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Drug Efficacy ◽  
Resistance Mechanisms ◽  
Therapeutic Strategies ◽  
Breast Cancer Stem Cells ◽  
Drug Resistant ◽  
Related Drug

Drug resistance is a major challenge in breast cancer (BC) treatment at present. Accumulating studies indicate that breast cancer stem cells (BCSCs) are responsible for the BC drugs resistance, causing relapse and metastasis in BC patients. Thus, BCSCs elimination could reverse drug resistance and improve drug efficacy to benefit BC patients. Consequently, mastering the knowledge on the proliferation, resistance mechanisms, and separation of BCSCs in BC therapy is extremely helpful for BCSCs-targeted therapeutic strategies. Herein, we summarize the principal BCSCs surface markers and signaling pathways, and list the BCSCs-related drug resistance mechanisms in chemotherapy (CT), endocrine therapy (ET), and targeted therapy (TT), and display therapeutic strategies for targeting BCSCs to reverse drug resistance in BC. Even more importantly, more attention should be paid to studies on BCSC-targeted strategies to overcome the drug resistant dilemma of clinical therapies in the future.

Methods to unravel the role of HDAC10 in autophagy-related drug resistance

2015 ◽  
Vol 227 (06/07) ◽  
Author(s):  
J Fabian ◽  
J Ridinger ◽  
O Witt ◽  
I Oehme
Keyword(s):  
Drug Resistance ◽  
Related Drug

Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

2020 ◽  
Vol 16 (34) ◽  
pp. 2863-2878
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Clinical Applications ◽  
Current Status ◽  
Cancer Drug ◽  
Genomic Alteration ◽  
Tumor Dna

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

scholarly journals Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (22) ◽  
pp. 32184-32199 ◽  
Author(s):  
Li Lv ◽  
Chunxia Liu ◽  
Chuxiong Chen ◽  
Xiaoxia Yu ◽  
Guanghui Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Receptor Targeting

scholarly journals Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple Negative Breast Cancer (TNBC) by Target Gene Network and Meta-Analysis

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 549
Author(s):  
Amal Qattan ◽  
Taher Al-Tweigeri ◽  
Wafa Alkhayal ◽  
Kausar Suleman ◽  
Asma Tulbah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Drug Response ◽  
Triple Negative ◽  
Meta Analysis ◽  
Integrated Analysis ◽  
Circulating Mirnas ◽  
Persistent Problem ◽  
Network Analyses

Resistance to therapy is a persistent problem that leads to mortality in breast cancer, particularly triple-negative breast cancer (TNBC). MiRNAs have become a focus of investigation as tissue-specific regulators of gene networks related to drug resistance. Circulating miRNAs are readily accessible non-invasive potential biomarkers for TNBC diagnosis, prognosis, and drug-response. Our aim was to use systems biology, meta-analysis, and network approaches to delineate the drug resistance pathways and clinical outcomes associated with circulating miRNAs in TNBC patients. MiRNA expression analysis was used to investigate differentially regulated circulating miRNAs in TNBC patients, and integrated pathway regulation, gene ontology, and pharmacogenomic network analyses were used to identify target genes, miRNAs, and drug interaction networks. Herein, we identified significant differentially expressed circulating miRNAs in TNBC patients (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, and miR-199a-3p) that regulate several molecular pathways (PAM (PI3K/Akt/mTOR), HIF-1, TNF, FoxO, Wnt, and JAK/STAT, PD-1/PD-L1 pathways and EGFR tyrosine kinase inhibitor resistance (TKIs)) involved in drug resistance. Through meta-analysis, we demonstrated an association of upregulated miR-93, miR-210, miR-19a, and miR-19b with poor overall survival outcomes in TNBC patients. These results identify miRNA-regulated mechanisms of drug resistance and potential targets for combination with chemotherapy to overcome drug resistance in TNBC. We demonstrate that integrated analysis of multi-dimensional data can unravel mechanisms of drug-resistance related to circulating miRNAs, particularly in TNBC. These circulating miRNAs may be useful as markers of drug response and resistance in the guidance of personalized medicine for TNBC.

scholarly journals LncRNA DLX6-AS1 Contributes to Epithelial–Mesenchymal Transition and Cisplatin Resistance in Triple-negative Breast Cancer via Modulating Mir-199b-5p/Paxillin Axis

2020 ◽  
Vol 29 ◽  
pp. 096368972092998 ◽  
Author(s):  
Chuang Du ◽  
Yan Wang ◽  
Yingying Zhang ◽  
Jianhua Zhang ◽  
Linfeng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer types with high recurrence, metastasis, and drug resistance. Recent studies report that long noncoding RNAs (lncRNAs)-mediated competing endogenous RNAs (ceRNA) play an important role in tumorigenesis and drug resistance of TNBC. Although elevated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) has been observed to promote carcinogenesis in various cancers, the role in TNBC remained unclear. In this study, expression levels of DLX6-AS1 were increased in TNBC tissues and cell lines when compared with normal tissues or breast fibroblast cells which were determined by quantitative real-time PCR (RT-qPCR). Then, CCK-8 assay, cell colony formation assay and western blot were performed in CAL-51 cells transfected with siRNAs of DLX6-AS1 or MDA-MB-231 cells transfected with DLX6-AS1 over expression plasmids. Knock down of DLX6-AS1 inhibited cell proliferation, epithelial-mesenchymal transition (EMT), decreased expression levels of BCL2 apoptosis regulator (Bcl-2), Snail family transcriptional repressor 1 (Snail) as well as N-cadherin and decreased expression levels of cleaved caspase-3, γ-catenin as well as E-cadherin, while up regulation of DLX6-AS1 had the opposite effect. Besides, knockdown of DLX6-AS1 in CAL-51 cells or up regulation of DLX6-AS1 in MDA-MB-231 cells also decreased or increased cisplatin resistance of those cells analyzed by MTT assay. Moreover, by using dual luciferase reporter assay, RNA immunoprecipitation and RNA pull down assay, a ceRNA which was consisted by lncRNA DLX6-AS1, microRNA-199b-5p (miR-199b-5p) and paxillin (PXN) was identified. And DLX6-AS1 function through miR-199b-5p/PXN in TNBC cells. Finally, results of xenograft experiments using nude mice showed that DLX6-AS1 regulated cell proliferation, EMT and cisplatin resistance by miR-199b-5p/PXN axis in vivo. In brief, DLX6-AS1 promoted cell proliferation, EMT, and cisplatin resistance through miR-199b-5p/PXN signaling in TNBC in vitro and in vivo.

scholarly journals Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1981
Author(s):  
Naheed Arfin Borah ◽  
Mamatha M. Reddy
Keyword(s):  
Drug Resistance ◽  
Cell Cycle Progression ◽  
Therapeutic Strategy ◽  
Tumor Development ◽  
Aurora Kinase ◽  
Aurora Kinase B ◽  
Development Therapy ◽  
Chromosomal Passenger ◽  
Combination Studies ◽  
Related Drug

Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression. Deregulation of AURKB is observed in several tumors and its overexpression is frequently linked to tumor cell invasion, metastasis and drug resistance. AURKB has emerged as an attractive drug target leading to the development of small molecule inhibitors. This review summarizes recent findings pertaining to the role of AURKB in tumor development, therapy related drug resistance, and its inhibition as a potential therapeutic strategy for cancer. We discuss AURKB inhibitors that are in preclinical and clinical development and combination studies of AURKB inhibition with other therapeutic strategies.

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