The fate of chemoresistance in triple negative breast cancer (TNBC).
The fate of chemoresistance in triple negative breast cancer (TNBC).
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DOI：
10.1016/j.bbacli.2015.03.003
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
McCann A
中科院分区：
文献类型：
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作者：
O'Reilly EA;Gubbins L;Sharma S;Tully R;Guang MH;Weiner-Gorzel K;McCaffrey J;Harrison M;Furlong F;Kell M;McCann A
由于缺乏治疗靶点，患有三阴性乳腺癌（TNBC）的女性的治疗选择有限，因此，使用标准化疗如紫杉醇（Taxol®）进行管理。化疗后，理想的肿瘤反应是凋亡性细胞死亡。化疗后，细胞可以通过经历活细胞应答（如细胞衰老）来维持活力，产生可以直接增强恶性表型的分泌体。肿瘤细胞如何保持活力，在化疗的参与进行了讨论。此外，我们还讨论了这种保留的肿瘤细胞活力在复发性和转移性TNBC疾病发展的背景下的影响。目前的辅助和新辅助治疗和正在研究的新的潜在疗法也进行了审查。细胞衰老和细胞保护性自噬是TNBC中化学抗性的潜在机制。这两种响应于化疗的非凋亡结果是密不可分的，并且是化疗竞技场中被忽视的研究结果。因此，细胞命运评估可能具有预测TNBC患者结果的潜力。关注癌细胞可以通过细胞衰老和细胞保护性自噬绕过对化疗的期望细胞凋亡反应的事实将突出靶向非凋亡存活途径以增强化疗功效的重要性。肿瘤细胞如何保留化疗后的活力进行了讨论。TNBC中肿瘤细胞活力的影响进行了讨论。目前正在研究的化学疗法和新疗法进行了审查。概述了TNBC的耐药机制和缺氧的作用。衰老和自噬是TNBC中化学抗性的潜在机制。
Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy. How tumour cells retain viability after chemotherapeutic engagement is discussed. The implications of tumour cell viability in TNBC are discussed. Chemotherapy and novel therapies that are currently being researched are reviewed. Chemoresistance mechanisms and hypoxia’s role in TNBC are outlined. Senescence and autophagy are potential mechanisms of chemoresistance in TNBC.