三阴性乳腺癌靶向治疗相关信号通路及其临床应用

三阴性乳腺癌(triple negative breast cancer, TNBC)占全部乳腺癌病例的15%~20%,其雌激素受体、孕激素受体和人表皮生长因子受体2均为阴性表达,也是所有乳腺癌亚型中侵袭性和恶性程度较高的一种。TNBC还具有较高的复发风险和较差的预后特性。由于异质性高、临床特征复杂,化疗、放疗和手术切除等手段仍是当前TNBC治疗的主要方法。然而,严重的副作用、高复发风险和健康损伤等问题仍然不容忽视。随着TNBC基础研究的进展,越来越多的TNBC靶向治疗相关信号通路被揭示,而且其中有一部分已进入临床试验,为TNBC的治疗提供了充满希望和前景的分子靶点。此外,其中一些治疗靶点在TNBC精确分型和精准治疗的临床实践中发挥着重要的作用。本文对TNBC靶向治疗中经典的合成致死通路、PI3K/AKT/mTOR通路、PD-1/PD-L1免疫通路等信号通路及其临床试验进行了综述,同时介绍了近几年比较具有潜力的TNBC靶向治疗信号通路,包括肿瘤血管生成通路、多胺合成和分解代谢通路、SLC3A2/LAT1通路以及IGF-1/IGF-1R/FAK/YAP信号转导通路等。

Signaling Pathways for the Targeted Therapy of Triple-Negative Breast Cancer and Their Clinical Applications

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer cases, with the negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC is a highly aggressive and malignant subtype, which also has a high risk of recurrence and poor prognosis. Due to its high heterogeneity and complicated clinical features, chemotherapy, radiotherapy, and surgical resection are the dominant methods for TNBC treatment currently. However, severe side effects, high risk of recurrence, and damages to health are not neglectable. With the progress of basic research on TNBC, more and more signaling pathways suitable for the targeted therapy of TNBC have been revealed, and some of them have successfully entered into clinical trials, suggesting promising molecular targets in TNBC treatment. Moreover, some of these theraputic targets play important roles in the classification and precise treatment of TNBC. This paper reviewed the research progress and clinical trials of the classic signaling pathways in the targeted therapy of TNBC, including synthetic lethality pathway, PI3K/AKT/mTOR pathway, PD-1/PD-L1 immune pathway, et al. Meanwhile, we also introduced potential signaling pathways revealed in recent years, including tumor angiogenesis pathway, polyamine synthesis and metabolism pathway, SLC3A2/LAT1 transportation pathway, and IGF-1/IGF-1R/FAK/YAP signal transduction pathway,et al.