Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs.
Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs.
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DOI：
10.3390/cancers13153697
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发表时间：
2021-07-23
期刊：
影响因子：
5.2
通讯作者：
Sharma D
中科院分区：
文献类型：
--
作者：
Wu Q;Siddharth S;Sharma D
三阴性乳腺癌（TNBC）是一种高度侵袭性的乳腺癌亚型，不能用内分泌疗法和Her 2靶向疗法治疗。虽然它在新诊断的乳腺癌中的患病率约为12.7%，但它占乳腺癌相关死亡率的40%。TNBC死亡率较高的部分原因是缺乏靶向治疗和对化疗产生耐药性。我们讨论了导致化疗耐药性的几种重要机制，并重点讨论了可能用于开发TNBC疗法的重要途径和生物学特征。TNBC目前被定义为不存在ER，PR和Her 2，TNBC的最大飞跃是我们能够用“x”蛋白的存在来表征它们。通过这篇综述，我们打算突出TNBC的关键节点，并推动该领域将TNBC的关键特征与新型药物之间的点连接起来。与TNBC相关的转移进展和肿瘤复发肯定是乳腺癌相关死亡率的主要原因;然而，TNBC化疗耐药性、转移和肿瘤复发的潜在机制仍然有些模糊。与其他乳腺癌亚型（82.7%至92.5%）相比，TNBC显示出77%的总体4年生存率。TNBC是乳腺癌的最具侵袭性的亚型，化疗是主要的批准治疗策略。ABC转运蛋白和DNA损伤反应基因的激活以及癌症干细胞的富集和化疗后的代谢重编程有助于选择化学抗性细胞，这主要是抗化疗方案失败的原因。这些选择的化学抗性细胞进一步导致远处转移和肿瘤复发。本综述讨论了已批准的标准治疗和化疗耐药性的靶向分子机制，并提供了有关TNBC管理最新进展的全面更新。
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that cannot be treated with endocrine therapy and Her2-targeted therapy. Although its prevalence among newly diagnosed breast cancers is approximately 12.7%, it accounts for 40% of breast cancer-related mortality. Higher mortality rates among TNBC is partly because of the lack of targeted therapies and the development of resistance to chemotherapy. We discuss several important mechanisms that lead to chemoresistance and focus on important pathways and biological features that can be potentially exploited to develop therapies for TNBC. TNBC is currently defined by the absence of ER, PR, and Her2 and the greatest leap for TNBC would be our ability to characterize them with the presence of ‘x’ proteins. With this review, we intend to highlight the key nodes of TNBC and push the field towards connecting the dots between key features of TNBC and novel drug(s). Metastatic progression and tumor recurrence pertaining to TNBC are certainly the leading cause of breast cancer-related mortality; however, the mechanisms underlying TNBC chemoresistance, metastasis, and tumor relapse remain somewhat ambiguous. TNBCs show 77% of the overall 4-year survival rate compared to other breast cancer subtypes (82.7 to 92.5%). TNBC is the most aggressive subtype of breast cancer, with chemotherapy being the major approved treatment strategy. Activation of ABC transporters and DNA damage response genes alongside an enrichment of cancer stem cells and metabolic reprogramming upon chemotherapy contribute to the selection of chemoresistant cells, majorly responsible for the failure of anti-chemotherapeutic regime. These selected chemoresistant cells further lead to distant metastasis and tumor relapse. The present review discusses the approved standard of care and targetable molecular mechanisms in chemoresistance and provides a comprehensive update regarding the recent advances in TNBC management.
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影响因子：
45.3
作者：
Atchley, Deann P.;Albarracin, Constance T.;Arun, Banu K.
通讯作者：
Arun, Banu K.
影响因子：
5.2
作者：
Bhattarai, Shristi;Klimov, Sergey;Aneja, Ritu
通讯作者：
Aneja, Ritu
影响因子：
45.3
作者：
Bardia, Aditya;Mayer, Ingrid A.;Vahdat, Linda T.
通讯作者：
Vahdat, Linda T.
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.8
作者：
Beaber, Elisabeth F.;Malone, Kathleen E.;Li, Christopher I.
通讯作者：
Li, Christopher I.