癌症耐药(英文)最新文献

{"title":"Exosomal miR-92b-5p regulates N4BP1 to enhance PTEN mono-ubiquitination in doxorubicin-resistant AML.","authors":"Qianyuan Li, Jie Cheng, Danni Qin, Sheng Xiao, Chenjiao Yao","doi":"10.20517/cdr.2024.140","DOIUrl":"https://doi.org/10.20517/cdr.2024.140","url":null,"abstract":"<p><p><b>Aim:</b> Doxorubicin, pivotal for acute myeloid leukemia (AML) treatment, often succumbs to resistance, impeding therapeutic success. Although exosomal transfer is linked to chemoresistance, the detailed role of exosomal miRNAs in doxorubicin resistance remains incompletely understood. <b>Methods:</b> We employed miRNA sequencing to delineate the profile of exosomal miRNAs in doxorubicin-resistant K562/DOX cells and AML patients. Subsequently, qPCR was utilized to scrutinize the expression of exosomal miR-92b-5p in these resistant cells and AML patients. A dual-luciferase reporter assay was conducted to elucidate the direct binding of miR-92b-5p to NEDD4 binding protein 1 (N4BP1). Furthermore, interactions between N4BP1 and NEDD4, as well as between NEDD4 and PTEN, were investigated by co-immunoprecipitation (Co-IP). Meanwhile, the ubiquitination of PTEN was also examined by Co-IP. Western blot analysis was applied to assess the expression levels of N4BP1, NEDD4, PTEN, RAD51, and proteins associated with the PI3K-AKT-mTOR pathway. Gain- and loss-of-function studies were conducted to ascertain the functional role of miR-92b-5p in doxorubicin resistance by using miR-92b-5p-mimic and miR-92b-5p-inhibitor transfections. <b>Results:</b> Our study found exosomal miR-92b-5p was upregulated both in doxorubicin-resistant cells and AML patients. Moreover, miR-92b-5p targets N4BP1, promoting NEDD4-mediated mono-ubiquitination of PTEN. This alters PTEN's subcellular localization, promoting nuclear PTEN and reducing cytoplasmic PTEN, which in turn leads to increased RAD51 for DNA repair and activation of the PI3K-AKT-mTOR pathway for cell proliferation, contributing to doxorubicin resistance. <b>Conclusion:</b> Our study reveals a novel mechanism of doxorubicin resistance mediated by exosomal miR-92b-5p and provides potential therapeutic targets for overcoming drug resistance in AML.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"16"},"PeriodicalIF":4.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813085","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}

{"title":"Circular RNAs modulate cancer drug resistance: advances and challenges.","authors":"Jinghan Hua, Zhe Wang, Xiaoxun Cheng, Jiaojiao Dai, Ping Zhao","doi":"10.20517/cdr.2024.195","DOIUrl":"https://doi.org/10.20517/cdr.2024.195","url":null,"abstract":"<p><p>Acquired drug resistance is a main factor contributing to cancer therapy failure and high cancer mortality, highlighting the necessity to develop novel intervention targets. Circular RNAs (circRNAs), an abundant class of RNA molecules with a closed loop structure, possess characteristics including high stability, which provide unique advantages in clinical application. Growing evidence indicates that aberrantly expressed circRNAs are associated with resistance against various cancer treatments, including targeted therapy, chemotherapy, radiotherapy, and immunotherapy. Therefore, targeting these aberrant circRNAs may offer a strategy to improve the efficiency of cancer therapy. Herein, we present a summary of the most recently studied circRNAs and their regulatory roles on cancer drug resistance. With the advances in artificial intelligence (AI)-based bioinformatics algorithms, circRNAs could emerge as promising biomarkers and intervention targets in cancer therapy.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"17"},"PeriodicalIF":4.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813068","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}

{"title":"Strategies to combat cancer drug resistance: focus on copper metabolism and cuproptosis.","authors":"Leyi Yao, Baoyi Jiang, Dacai Xu","doi":"10.20517/cdr.2025.41","DOIUrl":"https://doi.org/10.20517/cdr.2025.41","url":null,"abstract":"<p><p>Cancer cells often develop tolerance to chemotherapy, targeted therapy, and immunotherapy drugs either before or during treatment. The significant heterogeneity among various tumors poses a critical challenge in modern cancer research, particularly in overcoming drug resistance. Copper, as an essential trace element in the body, participates in various biological processes of diseases, including cancers. The growth of many types of tumor cells exhibits a heightened dependence on copper. Thus, targeting copper metabolism or inducing cuproptosis may be potential ways to overcome cancer drug resistance. Copper chelators have shown potential in overcoming cancer drug resistance by targeting copper-dependent processes in cancer cells. In contrast, copper ionophores, copper-based nanomaterials, and other small molecules have been used to induce copper-dependent cell death (cuproptosis) in cancer cells, including drug-resistant tumor cells. This review summarizes the regulation of copper metabolism and cuproptosis in cancer cells and the role of copper metabolism and cuproptosis in cancer drug resistance, providing ideas for overcoming cancer resistance in the future.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"15"},"PeriodicalIF":4.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813093","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}

{"title":"Unraveling <i>BRAF</i> alterations: molecular insights to circumvent therapeutic resistance across cancer types.","authors":"Caterina Perfetto, Marianna Aprile, Simona Cataldi, Elisa Giovannetti, Valerio Costa","doi":"10.20517/cdr.2024.213","DOIUrl":"https://doi.org/10.20517/cdr.2024.213","url":null,"abstract":"<p><p><b>Aim:</b> As intrinsic resistance - often driven by concurrent genomic alterations in tumor suppressor genes or oncogenes - remains a major challenge in oncology, this work aimed to comprehensively analyze <i>BRAF</i> somatic alterations across cancer types and identify new potential therapeutic strategies to overcome drug resistance. <b>Methods:</b> We conducted an extensive analysis of genomics, transcriptomics, and clinical data retrieved from public repositories, including cBioPortal. Our comprehensive analysis examined <i>BRAF</i> alterations [point mutations, structural variants (SVs) and copy number alteration] in more than 217,000 tumor samples across 120 distinct tumor types from primary and metastatic sites in both adult and pediatric cohorts, focusing on mutual exclusivity and co-occurrence of mutations in other oncogenes or tumor suppressors. The work also explores the association of <i>BRAF</i> somatic alterations with survival, clinical and molecular features. <b>Results:</b> Analysis of mutation frequencies across cancer types revealed that BRAFV600E represents approximately 90% of all <i>BRAF</i> alterations. While melanoma and thyroid carcinoma show the highest prevalence of <i>BRAF</i> mutations, followed by colorectal and non-small cell lung cancer in terms of absolute number of patients harboring <i>BRAF</i> mutations worldwide, notably high mutation frequencies were identified in rare malignancies, including hairy-cell leukemia, ganglioglioma, and serous borderline ovarian tumors. The comprehensive analysis of genomic profiling data across these tumors uncovered distinct patterns of co-occurring and mutually exclusive alterations in oncogenes and tumor suppressor genes, illuminating resistance mechanisms and suggesting novel therapeutic combinations. <b>Conclusion:</b> Comprehensive genomic profiling is critical for optimizing targeted therapy and overcoming drug resistance in <i>BRAF</i>-mutated cancers. The identification of co-occurring alterations provides opportunities for rational combination therapies, emphasizing the importance of detailed mutation profiling in developing effective treatment strategies across diverse cancer types.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"14"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813123","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}

{"title":"Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways.","authors":"Chi Teng, Jia-Wen Chen, Li-Sha Shen, Sibao Chen, Guo-Qing Chen","doi":"10.20517/cdr.2024.178","DOIUrl":"https://doi.org/10.20517/cdr.2024.178","url":null,"abstract":"<p><p>Cancer remains a significant global health challenge, with current chemotherapeutic strategies frequently limited by the emergence of resistance. In this context, natural compounds with the potential to overcome resistance have garnered considerable attention. Among these, sesquiterpene lactones, primarily derived from plants in the Asteraceae family, stand out for their potential anticancer properties. This review specifically focuses on five key signaling pathways: PI3K/Akt/mTOR, NF-κB, Wnt/β-catenin, MAPK/ERK, and STAT3, which play central roles in the mechanisms of cancer resistance. For each of these pathways, we detail their involvement in both cancer development and the emergence of drug resistance. Additionally, we investigate how sesquiterpene lactones modulate these pathways to overcome resistance across diverse cancer types. These insights highlight the potential of sesquiterpene lactones to drive the advancement of novel therapies that can effectively combat both cancer progression and drug resistance.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"13"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813088","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}

{"title":"The epigenetic mechanisms involved in the treatment resistance of glioblastoma.","authors":"Aanya Shahani, Hasan Slika, Ahmad Elbeltagy, Alexandra Lee, Christopher Peters, Toriyn Dotson, Divyaansh Raj, Betty Tyler","doi":"10.20517/cdr.2024.157","DOIUrl":"https://doi.org/10.20517/cdr.2024.157","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an aggressive malignant brain tumor with almost inevitable recurrence despite multimodal management with surgical resection and radio-chemotherapy. While several genetic, proteomic, cellular, and anatomic factors interplay to drive recurrence and promote treatment resistance, the epigenetic component remains among the most versatile and heterogeneous of these factors. Herein, the epigenetic landscape of GBM refers to a myriad of modifications and processes that can alter gene expression without altering the genetic code of cancer cells. These processes encompass DNA methylation, histone modification, chromatin remodeling, and non-coding RNA molecules, all of which have been found to be implicated in augmenting the tumor's aggressive behavior and driving its resistance to therapeutics. This review aims to delve into the underlying interactions that mediate this role for each of these epigenetic components. Further, it discusses the two-way relationship between epigenetic modifications and tumor heterogeneity and plasticity, which are crucial to effectively treat GBM. Finally, we build on the previous characterization of epigenetic modifications and interactions to explore specific targets that have been investigated for the development of promising therapeutic agents.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"12"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813099","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}

{"title":"Antibody-drug conjugates in breast cancer treatment: resistance mechanisms and the role of therapeutic sequencing.","authors":"Émilie Audrey Larose, Xinying Hua, Silin Yu, Amritha Thulaseedharan Pillai, Zongbi Yi, Haijun Yu","doi":"10.20517/cdr.2024.180","DOIUrl":"https://doi.org/10.20517/cdr.2024.180","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are a transformative approach in breast cancer therapy, offering targeted treatment with reduced toxicity by selectively delivering cytotoxic agents to cancer cells. While ADCs like trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan have shown significant efficacy, resistance mechanisms such as antigen loss, impaired internalization, and efflux of cytotoxic payloads challenge their effectiveness. This review discusses these resistance mechanisms and explores advanced strategies to overcome them, including innovations in linker chemistry, multi-antigen targeting, and biomarker-driven personalization. Additionally, therapeutic sequencing - determining the optimal order of ADCs with other treatments such as chemotherapy, endocrine therapy, and immunotherapy - is examined as a crucial approach to maximize ADC efficacy and manage resistance. Evidence-based sequencing strategies, particularly for human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC), are supported by clinical trials demonstrating the benefits of ADCs in both early-stage and metastatic settings. The potential of combination therapies, such as ADCs with immune checkpoint inhibitors (ICIs), further highlights the evolving landscape of breast cancer treatment. As ADC technology advances, personalized approaches integrating biomarkers and optimized sequencing protocols offer promising avenues to enhance treatment outcomes and combat resistance in breast cancer.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"11"},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813062","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}

{"title":"Sophisticated roles of tumor microenvironment in resistance to immune checkpoint blockade therapy in hepatocellular carcinoma.","authors":"Yi-Zhe Zhang, Yunshu Ma, Ensi Ma, Xizhi Chen, Yue Zhang, Baobing Yin, Jing Zhao","doi":"10.20517/cdr.2024.165","DOIUrl":"10.20517/cdr.2024.165","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a serious threat to global health, with rising incidence and mortality rates. Therapeutic options for advanced HCC are quite limited, and the overall prognosis remains poor. Recent advancements in immunotherapy, particularly immune-checkpoint blockade (ICB) targeting anti-PD1/PD-L1 and anti-CTLA4, have facilitated a paradigm shift in cancer treatment, demonstrating substantial survival benefits across various cancer types, including HCC. However, only a subset of HCC patients exhibit a favorable response to ICB therapy, and its efficacy is often hindered by the development of resistance. There are many studies to explore the underlying mechanisms of ICB response. In this review, we compiled the latest progression in immunotherapies for HCC and systematically summarized the sophisticated mechanisms by which components of the tumor microenvironment (TME) regulate resistance to ICB therapy. Additionally, we also outlined some scientific rationale strategies to boost antitumor immunity and enhance the efficacy of ICB in HCC. These insights may serve as a roadmap for future research and help improve outcomes for HCC patients.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"10"},"PeriodicalIF":4.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574850","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}

{"title":"Overcoming drug resistance in castrate-resistant prostate cancer: current mechanisms and emerging therapeutic approaches.","authors":"Adam Khorasanchi, Feng Hong, Yuanquan Yang, Eric A Singer, Peng Wang, Mingjia Li, Linghua Zheng, Paul Monk, Amir Mortazavi, Lingbin Meng","doi":"10.20517/cdr.2024.173","DOIUrl":"10.20517/cdr.2024.173","url":null,"abstract":"<p><p>Metastatic castration-resistant prostate cancer (mCRPC) is driven by a complex network of resistance mechanisms against standard-of-care therapies, resulting in poor long-term outcomes. This review offers a uniquely comprehensive and integrative perspective on these resistance pathways, systematically examining both androgen receptor (AR)-dependent factors (including AR overexpression, point mutations, glucocorticoid receptor signaling, splice variants, post-translational modifications, altered coregulators, and intratumoral hormone biosynthesis) and AR-independent pathways (such as neuroendocrine differentiation, lineage plasticity, and alternative growth factor signaling). We also highlight resistance mechanisms influencing immunotherapy, chemotherapy, radiopharmaceutical therapy and targeted therapy. By synthesizing emerging insights across these domains, this review not only clarifies the underlying biology of mCRPC resistance but also identifies key leverage points for more effective interventions. Building on this foundation, we propose a forward-looking framework for overcoming mCRPC drug resistance, emphasizing the importance of biomarker-guided patient selection, combination strategies that simultaneously target multiple resistance mechanisms, and novel therapies under investigation. These recommendations are intended to guide future clinical trial designs and research priorities that move beyond incremental improvements. Ultimately, this comprehensive synthesis aims to serve as a resource for clinicians and researchers to accelerate the development of durable, precision-based treatment strategies in mCRPC.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"9"},"PeriodicalIF":4.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574828","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}

{"title":"Exploring YAP1-related TIME in SCLC: implications for survival and treatment response to immuno-chemotherapy.","authors":"Yu-Qing Chen, Jia-Xiong Tan, Ling-Ling Gao, Jia-Xing Yang, Jie Huang, Jin-Ji Yang, Qiang Zhao","doi":"10.20517/cdr.2024.177","DOIUrl":"10.20517/cdr.2024.177","url":null,"abstract":"<p><p><b>Aim:</b> Small-cell lung cancer (SCLC) is usually diagnosed as an advanced stage with a poor outcome. SCLC has limited response to immunotherapy due to the absence or lack of immune cell infiltration, so studying its tumor immune microenvironment (TIME) is essential. <b>Methods:</b> The study involved patients with extensive-stage small-cell lung cancer (ES-SCLC) diagnosed at the Guangdong Lung Cancer Institute between January 2018 and April 2022 who had received the atezolizumab/carboplatin/etoposide (ECT) treatment. We used multi-immunohistochemistry (mIHC) to assess the prognostic value of YAP1 and TIME in SCLC, with results confirmed using public data. <b>Results:</b> 15 patients with sufficient baseline biopsy samples were included in this study. The total population of YAP1-positive cells is inversely related to progression-free survival (PFS) and shows a potential negative correlation with overall survival (OS). CD56-positive cells are the primary components of TIME in SCLC tumor parenchyma and stroma. The total population and cell density of YAP1-positive cells are significantly positively correlated with CD4-positive cells. Furthermore, in the tumor parenchyma, both the proportion and the cell density of YAP1-positive cells are positively correlated with that of FOXP3-positive cells. The total population of CD56-positive cells showed a negative correlation trend with YAP1-positive cells but without significant difference. <b>Conclusion:</b> YAP1 has shown prognostic value in SCLC patients receiving ECT regimen treatment. The high expression level of YAP1 seems related to the inhibitory TIME. However, some prospective studies with larger populations are warranted.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"8"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574776","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}