Carmine Valenza, Renato Maria Marsicano, Dario Trapani, Giuseppe Curigliano
{"title":"PARP 抑制剂耐药的 BRCA 基因突变晚期乳腺癌：现状与新兴疗法。","authors":"Carmine Valenza, Renato Maria Marsicano, Dario Trapani, Giuseppe Curigliano","doi":"10.1097/CCO.0000000000001092","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Patients with advanced breast cancer (aBC) treated with PARP inhibitors (PARPi) can eventually experience disease progression for emerging treatment resistance. This review aims to depict the treatment the molecular landscape, and the innovative therapies for patients with PARPi-resistant BRCA-mutated aBC.</p><p><strong>Recent findings: </strong>No specific therapy is specifically available in the setting post-PARPi-failure, with antibody-drug conjugates or nonplatinum-based chemotherapy (PBC) representing the best treatment options in this setting. Mechanisms of on-target PARPi resistance can be classified in reversions (60%) and nonreversion (40%); reverse mutations restore PARP functions. According to the first evidence of clinical validity, these alterations are associated with lower efficacy of PARPi and PBC. However, their clinical utility needs to be assessed.</p><p><strong>Summary: </strong>PARPi-resistant aBC represents a clinical unmet need due to the lack of specific targeted therapies and validated prognostic and predictive biomarkers. Constant efforts are required to better define the mechanisms of PARPi resistance and, consequently, develop biomarker-based treatment approach to prevent or overcame resistance.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PARP inhibitor resistant BRCA-mutated advanced breast cancer: current landscape and emerging treatments.\",\"authors\":\"Carmine Valenza, Renato Maria Marsicano, Dario Trapani, Giuseppe Curigliano\",\"doi\":\"10.1097/CCO.0000000000001092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>Patients with advanced breast cancer (aBC) treated with PARP inhibitors (PARPi) can eventually experience disease progression for emerging treatment resistance. This review aims to depict the treatment the molecular landscape, and the innovative therapies for patients with PARPi-resistant BRCA-mutated aBC.</p><p><strong>Recent findings: </strong>No specific therapy is specifically available in the setting post-PARPi-failure, with antibody-drug conjugates or nonplatinum-based chemotherapy (PBC) representing the best treatment options in this setting. Mechanisms of on-target PARPi resistance can be classified in reversions (60%) and nonreversion (40%); reverse mutations restore PARP functions. According to the first evidence of clinical validity, these alterations are associated with lower efficacy of PARPi and PBC. However, their clinical utility needs to be assessed.</p><p><strong>Summary: </strong>PARPi-resistant aBC represents a clinical unmet need due to the lack of specific targeted therapies and validated prognostic and predictive biomarkers. Constant efforts are required to better define the mechanisms of PARPi resistance and, consequently, develop biomarker-based treatment approach to prevent or overcame resistance.</p>\",\"PeriodicalId\":10893,\"journal\":{\"name\":\"Current Opinion in Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Opinion in Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CCO.0000000000001092\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CCO.0000000000001092","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
PARP inhibitor resistant BRCA-mutated advanced breast cancer: current landscape and emerging treatments.
Purpose of review: Patients with advanced breast cancer (aBC) treated with PARP inhibitors (PARPi) can eventually experience disease progression for emerging treatment resistance. This review aims to depict the treatment the molecular landscape, and the innovative therapies for patients with PARPi-resistant BRCA-mutated aBC.
Recent findings: No specific therapy is specifically available in the setting post-PARPi-failure, with antibody-drug conjugates or nonplatinum-based chemotherapy (PBC) representing the best treatment options in this setting. Mechanisms of on-target PARPi resistance can be classified in reversions (60%) and nonreversion (40%); reverse mutations restore PARP functions. According to the first evidence of clinical validity, these alterations are associated with lower efficacy of PARPi and PBC. However, their clinical utility needs to be assessed.
Summary: PARPi-resistant aBC represents a clinical unmet need due to the lack of specific targeted therapies and validated prognostic and predictive biomarkers. Constant efforts are required to better define the mechanisms of PARPi resistance and, consequently, develop biomarker-based treatment approach to prevent or overcame resistance.
期刊介绍：
With its easy-to-digest reviews on important advances in world literature, Current Opinion in Oncology offers expert evaluation on a wide range of topics from sixteen key disciplines including sarcomas, cancer biology, melanoma and endocrine tumors. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by annotated references detailing the merits of the most important papers.
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