Breast Cancer : Targets and Therapy最新文献

{"title":"Immunotherapy: Constructive Approach for Breast Cancer Treatment.","authors":"Umer Anayyat, Faiza Ahad, Tobias Achu Muluh, Syed Aqib Ali Zaidi, Faiza Usmani, Hua Yang, Mengqing Li, Hammad Ali Hassan, Xiaomei Wang","doi":"10.2147/BCTT.S424624","DOIUrl":"10.2147/BCTT.S424624","url":null,"abstract":"<p><p>A novel and rapid therapeutic approach is the treatment of human breast cancer by enhancing the host's immune system. In initial findings, program death one (PD-1) and program cell death ligand one (PD-L1) showed positive results towards solid tumors, but tumor relapse and drug resistance are the major concerns. Breast cancer therapy has been transformed by the advent of immune checkpoint blockades (ICBs). Triple-negative breast cancers (TNBCs) have exhibited enduring responses to clinical usage of immune checkpoint inhibitors (ICBs) like atezolizumab and pembrolizumab. Nonetheless, a notable proportion of individuals with TNBC do not experience advantages from these treatments, and there is limited comprehension of the resistance mechanisms. Another approach to overcome resistance is cancer stem cells (CSCs), as these cells are crucial for the initiation and growth of tumors in the body. Various cancer vaccines are created using stem cells (dendritic, whole cell, bacterial) and focus primarily on targeting tumor-related antigens. The ultimate objective of cancer vaccines is to immunize the patients by active artificial immunity against cancer, though. In this review, we primarily focused on existing immunotherapeutic options, immune checkpoint blockers, the latest progress in understanding the molecular mechanisms underlying resistance to immune checkpoint inhibitors (ICBs), advanced strategies to overcome resistance to ICBs, cancer stem cell antigens and molecular markers, ongoing clinical trials for BCs and cancer vaccines for breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"925-951"},"PeriodicalIF":2.6,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer Awareness Among Women in Saudi Arabia: A Systematic Review.","authors":"Bassam AlRajhi, Faisal F Aljadani, Shahad Rafed Almarwan, Atheer Abdullah Alzahrani, Mostafa Hatim M Sindi, Abdulaziz Kano, Raghad Saleh Alzahrani, Rasha Baaqeel","doi":"10.2147/BCTT.S426079","DOIUrl":"https://doi.org/10.2147/BCTT.S426079","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer (BC) is the most prevalent cancer worldwide, and second most common cause of cancer-related deaths among women worldwide. Early detection of BC significantly improves prognosis; thus, awareness is an important aspect of BC morbidity and survival as well as the economic burden. This systematic review aimed to explore awareness of BC among women in Saudi Arabia.</p><p><strong>Patients and methods: </strong>A systematic search was performed using Medline, Scopus, the Directory of Open Access Journals (DOAJ), and Google Scholar for all cross-sectional studies conducted in Saudi Arabia, published after the year 2000 and in English. The quality assessment of the included studies was performed using the AXIS tool.</p><p><strong>Results: </strong>The total number of included articles after full-text assessment was 13 articles that were conducted between 2005 and 2022. The sample size of all the articles was 7,562 women. All the studies categorized BC awareness into low, moderate, and high groups. The level of low awareness among women reached 66.3% (n=2808), 13.5% (n=570) had moderate awareness levels, and 20.2% (n=858) had high awareness levels. Furthermore, 59.4% (n=1446) of the participants did not perform breast self-examination (BSE) regularly.</p><p><strong>Conclusion: </strong>The level of awareness and knowledge regarding BC and BSE was significantly low among women in Saudi Arabia, as all included studies except one have indicated. We highly recommend and urge the implementation of effective special programs and campaigns to raise awareness regarding BC and integrating BSE into school health programs dedicated to women living in Saudi Arabia.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"913-924"},"PeriodicalIF":2.6,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10726713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potent Novel CDK4/6 Inhibitor TQB3616 in Hormone Receptor Positive Breast Cancer: Preclinical Characterization with in vitro and Human Tumor Xenograft Models.","authors":"Wenyu Hu, Lei Wang, JiaLing Luo, Jian Zhang, Nanlin Li","doi":"10.2147/BCTT.S434973","DOIUrl":"https://doi.org/10.2147/BCTT.S434973","url":null,"abstract":"<p><strong>Purpose: </strong>Inhibition of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) pathway exerts a considerable inhibitory effect, preventing the spread and metastasis of breast cancer cells and promoting tumor regression. In this study, we examined the antitumor activity of TQB3616, a novel inhibitor of CDK4/6 activity, which showed a greater efficacy improvement in antitumor effects.</p><p><strong>Methods: </strong>TQB3616 group, abemaciclib group and endocrine or HER-2 targeted combination therapy group were set up respectively. The effects of drugs on cell proliferation activity, cell cycle, apoptosis, downstream protein expression and gene expression of HR positive (T47D, MCF-7) and HER-2 positive (BT474, MDA-MB-361) breast cancer cell lines were studied. The antiproliferative effect of TQB3616 was also measured in vivo.</p><p><strong>Results: </strong>TQB3616 showed a remarkable inhibitory effect on the proliferation of hormone receptor-positive breast cancer cells in vitro. In addition, TQB3616 combined with endocrine therapy or Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy showed significant synergistic antitumor activity in estrogen receptor (ER)-positive/HER2-negative or HER2-positive breast cancer. In contrast to abemaciclib, which targets the CDK4/6 pathway with proven efficacy, the oral agent TQB3616 not only induced G1 stalling, leading to a profound reduction in the level of RB protein phosphorylated at Ser807/811, but also showed enhanced tumor killing effects by promoting cell apoptosis. Oral administration of TQB3616 showed more potent antitumor activity than abemaciclib in an in vitro breast cancer xenograft model, causing significant tumor regression associated with sustained target inhibition in tumor tissue and manageable in vivo toxicity.</p><p><strong>Conclusion: </strong>The results of this study indicate that TQB3616 is a novel CDK4/6 inhibitor, and its highly effective antitumor activity against breast cancer is expected to yield promising therapeutic effects in clinical studies.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"899-912"},"PeriodicalIF":2.6,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram Based on Super-Resolution Ultrasound Images Outperforms in Predicting Benign and Malignant Breast Lesions","authors":"Liu Yang, Zhe Ma","doi":"10.2147/BCTT.S435510","DOIUrl":"https://doi.org/10.2147/BCTT.S435510","url":null,"abstract":"Objective To establish a good predictive model using a deep-learning (DL)-based three-dimensional (3D) super-resolution ultrasound images for the diagnosis of benign and malignant breast lesions. Methods This retrospective study included 333 patients with histopathologically confirmed breast lesions, randomly split into training (N=266) and testing (N=67) datasets. Eight models, including four deep learning models (ORResNet101, ORMobileNet_v2, SRResNet101, SRMobileNet_v2) and four machine learning models (OR_LR, OR_SVM, SR_LR, SR_SVM), were developed based on original and super-resolution images. The best performing model was SRMobileNet_v2, which was used to construct a nomogram integrating clinical factors. The performance of nomogram was evaluated using receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and calibration curves. Results SRMobileNet_v2, MobileNet_V2 based on super-resolution ultrasound images, had the best predictive performance in four traditional machine learning models and four deep learning models, with AUC improvements of 0.089 and 0.031 in the training and testing sets, relative to the ORMobileNet_v2 model based on original ultrasound images. The deep-learning nomogram was constructed using the SRMobileNet_v2 model score, tumor size, and patient age, resulting in superior predictive efficacy compared to the nomogram without the SRMobileNet_v2 model score. Furthermore, it demonstrated favorable calibration, discrimination, and clinical utility in both cohorts. Conclusion The diagnostic prediction model utilizing super-resolution reconstructed ultrasound images outperforms the model based on original images in distinguishing between benign and malignant breast lesions. The nomogram based on super-resolution ultrasound images has the potential to serve as a reliable auxiliary diagnostic tool for clinicians, exhibiting superior predictive performance in distinguishing between benign and malignant breast lesions.","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" 6","pages":"867 - 878"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138615519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accuracy Rate of Methylene Blue Injection in Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer Patients: A Prospective Observational Study","authors":"Harlan Kasyfil Aziz, Y. Azhar, I. R. Widarda, M. Abdurahman, Zuldi Erdiansyah, Prapanca Nugraha, K. Lukman","doi":"10.2147/BCTT.S439325","DOIUrl":"https://doi.org/10.2147/BCTT.S439325","url":null,"abstract":"Objective Breast cancer is the most prevalent cancer in women and can spread to the lymph nodes in the axilla. The sentinel lymph node is the first lymph node to be targeted for the spread or metastasis of cancer cells involving the lymph nodes. The aim of this study is to compare the accuracy rate of methylene blue injection into sentinel lymph nodes in early-stage breast cancer patients who have undergone incisional and excisional biopsies. Methods This is a prospective observational study conducted in two general hospitals in West Java, Indonesia. The research subjects in this study were early-stage breast cancer patients with no lymph node metastasis (N0) who had undergone a biopsy. There were 83 study subjects included in this study. The sentinel lymph node biopsy was taken after injection of methylene blue into the peritumoral area. Blue nodes in the axilla were marked as positive lymph node biopsy results and sent for histopathology examination. Results Patients who underwent excisional biopsy surgery had a sensitivity rate of 85.3% and a specificity of 93.3%, while the accuracy rate in patients who underwent incisional biopsy surgery had a sensitivity rate of 79.2% and a specificity of 80%. Conclusion There was no difference in the accuracy of SLNB using methylene blue in patients with early-stage breast cancer with N0 who had a history of incisional and excisional biopsy.","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" 2","pages":"891 - 897"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138621115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Cytotoxicity of the Methanolic Extract of Red Sea Marine Sponge Xestospongia Testudinaria and Its Related Compounds Against MCF-7 Human Breast Cancer Cells","authors":"Faris A Alkhilaiwi, Sana Fadil, Fadwa Aljoud, Ahmed Yonbawi, Abrar Ashi, Rawan H Hareeri, S. Bakhashab, Ahmad Alamri, Ahmed Albikairi, L. Shaala, Ali El-Gamal, Diaa Youssef","doi":"10.2147/BCTT.S429721","DOIUrl":"https://doi.org/10.2147/BCTT.S429721","url":null,"abstract":"Background Breast cancer is a leading cause of death and one of the most common fatal medical conditions in the world. Chemical compounds of various types have been identified in the Red Sea marine sponge Xestospongia testudinaria, including sterol esters, sterols, indole alkaloids, and brominated polyunsaturated fatty acids. These compounds have demonstrated promising biological features, which in cludes anti-inflammatory, cancer preventive, and antioxidant capacities. Methods The cytotoxic potential of Xestospongia testudinaria was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and morphological alterations in MCF-7 cell line. Furthermore, the flow cytometry was also utilized to assess apoptosis and identify changes in the cell cycle; besides, cell migration was assessed by scratch wound-healing assay. Results A significant dose-dependent decrease in the percentage of MCF-7 cell viability was observed with IC50 39.8 ug/mL. Functional studies were performed on MCF-7 to show that Xestospongia testudinaria raises apoptotic cell death and induces growth arrest at the G1/G0 while inhibiting cell migration in scratch assay. Conclusion These results demonstrated that Xestospongia testudinaria extract has an inhibitory effect on breast cancer cells proliferation, migration and induce apoptosis. Thus, it holds great promise as a potential treatment for breast cancer.","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" 4","pages":"879 - 890"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Radiotherapy Combined with Pyrotinib in the Treatment of HER2-Positive Breast Cancer with Brain Metastases.","authors":"Jie Huang, Wenqiang Zhu, Qiangzhi Duan, Chaomang Zhu, Xueling Shi, Hongyu Zhao, Peng Cai, Duojie Li","doi":"10.2147/BCTT.S440427","DOIUrl":"10.2147/BCTT.S440427","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM).</p><p><strong>Patients and methods: </strong>This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR).</p><p><strong>Results: </strong>The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B.</p><p><strong>Conclusion: </strong>For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"841-853"},"PeriodicalIF":3.3,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Real-World Treatment Patterns and Clinical Outcomes in Patients with Metastatic Breast Cancer Treated with Eribulin After Prior Immuno-Oncology or Antibody-Drug Conjugate Therapy.","authors":"Ravi K Goyal, Jingchuan Zhang, Keith L Davis, Martina Sluga-O'Callaghan, Peter A Kaufman","doi":"10.2147/BCTT.S422025","DOIUrl":"https://doi.org/10.2147/BCTT.S422025","url":null,"abstract":"<p><strong>Introduction: </strong>Eribulin was approved by the FDA in 2010 for the treatment of metastatic breast cancer (MBC) in the United States (US). More recently, several immuno-oncology (IO) and antibody-drug conjugate (ADC) regimens have been approved for MBC. We assessed the treatment patterns and clinical outcomes in MBC patients treated with eribulin following treatment with an IO or ADC in US clinical practice.</p><p><strong>Materials and methods: </strong>In a retrospective patient medical chart review study, patients with MBC, aged ≥18 years, who initiated eribulin therapy between March 1, 2019, and September 30, 2020, treated with either prior IO or ADC in the metastatic setting were included. Patient demographics, treatment characteristics, and clinical outcomes were analyzed descriptively. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier analyses.</p><p><strong>Results: </strong>In the study population (N=143), median age at eribulin initiation was 62 years; 64% were Caucasian, and 67% had triple-negative MBC (TNBC). Eribulin therapy was used in the second to fifth line of therapy in the metastatic setting; median treatment duration was 7.2 months. The overall response rate for eribulin was 59.4%. Median rwPFS and OS from eribulin initiation were 21.4 months (95% CI, 12.9-not estimable [NE]) and 24.2 months (95% CI, 17.5-NE), respectively. In patients with TNBC, median rwPFS and OS from eribulin initiation were 12.0 months (95% CI, 8.8-NE) and 18.3 months (95% CI, 14.9-NE), respectively.</p><p><strong>Conclusion: </strong>These real-world data provide evidence for the clinical effectiveness outcomes of eribulin treatment among MBC patients previously treated with an IO or ADC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"855-865"},"PeriodicalIF":2.6,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications.","authors":"Jie Li, Dejiao He, Yajun Bi, Shengxuan Liu","doi":"10.2147/BCTT.S432750","DOIUrl":"https://doi.org/10.2147/BCTT.S432750","url":null,"abstract":"<p><p>Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20-23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"825-840"},"PeriodicalIF":2.6,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Advantage of Targeting PRMT5 in Combination with Chemotherapies or EGFR/HER2 Inhibitors in Triple-Negative Breast Cancers.","authors":"Rayan Dakroub, Solène Huard, Yara Hajj-Younes, Samyuktha Suresh, Bassam Badran, Hussein Fayyad-Kazan, Thierry Dubois","doi":"10.2147/BCTT.S430513","DOIUrl":"10.2147/BCTT.S430513","url":null,"abstract":"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subgroup characterized by a high risk of resistance to chemotherapies and high relapse potential. TNBC shows inter-and intra-tumoral heterogeneity; more than half expresses high EGFR levels and about 30% are classified as HER2-low breast cancers. High PRMT5 mRNA levels are associated with poor prognosis in TNBC and inhibiting PRMT5 impairs the viability of subsets of TNBC cell lines and delays tumor growth in TNBC mice models. TNBC patients may therefore benefit from a treatment targeting PRMT5. The aim of this study was to assess the therapeutic benefit of combining a PRMT5 inhibitor with different chemotherapies used in the clinics to treat TNBC patients, or with FDA-approved inhibitors targeting the HER family members.</p><p><strong>Methods: </strong>The drug combinations were performed using proliferation and colony formation assays on TNBC cell lines that were sensitive or resistant to EPZ015938, a PRMT5 inhibitor that has been evaluated in clinical trials. The chemotherapies analyzed were cisplatin, doxorubicin, camptothecin, and paclitaxel. The targeted therapies tested were erlotinib (EGFR inhibitor), neratinib (EGFR/HER2/HER4 inhibitor) and tucatinib (HER2 inhibitor).</p><p><strong>Results: </strong>We found that PRMT5 inhibition synergized mostly with cisplatin, and to a lesser extent with doxorubicin or camptothecin, but not with paclitaxel, to impair TNBC cell proliferation. PRMT5 inhibition also synergized with erlotinib and neratinib in TNBC cell lines, especially in those overexpressing EGFR. Additionally, a synergistic interaction was observed with neratinib and tucatinib in a HER2-low TNBC cell line as well as in a HER2-positive breast cancer cell line. We noticed that synergy can be obtained in TNBC cell lines that were resistant to PRMT5 inhibition alone.</p><p><strong>Conclusion: </strong>Altogether, our data highlight the therapeutic potential of targeting PRMT5 using combinatorial strategies for the treatment of subsets of TNBC patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"785-799"},"PeriodicalIF":2.6,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}