Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer which lacks oestrogen receptors, progesterone receptors and HER2 amplification, thereby making it difficult to target therapeutically. In addition, TNBC has the highest rates of metastatic disease and the poorest overall survival of all breast cancer subtypes. Resultantly, development of targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular characterisation of TNBCs have revealed various emerging therapeutic targets including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoints, androgen receptor and epigenetic proteins. Key successes include that of the PARP inhibitor, olaparib, which prolonged progression-free survival in a trial of BRCA-mutated breast cancer and for which clinical approval (in this setting) appears imminent. Nevertheless, the heterogeneity of TNBC has limited the clinical benefits of many trialled therapies in ‘unselected’ patients. Further, drug resistance develops following use of many targeted monotherapies due to upregulation of compensatory signalling pathways. In this review, we evaluate the current status of investigational targeted treatments and present evidence for the role of novel biomarkers and combination therapies in increasing response rates and circumventing drug-induced resistance. Additionally, we discuss promising novel targets in metastatic TNBC identified through preclinical and/or epidemiological studies.

三阴性乳腺癌（TNBC）是一种复杂且具有侵略性的乳腺癌亚型，缺乏雌激素受体，孕激素受体和HER2扩增，因此难以靶向治疗。此外，TNBC在所有乳腺癌亚型中均具有最高的转移性疾病发生率和最差的总体生存率。结果，迫切需要开发针对TNBC的靶向疗法。针对TNBCs分子表征的最新研究表明，各种新兴的治疗靶标包括PARP1，受体和非受体酪氨酸激酶，免疫检查点，雄激素受体和表观遗传蛋白。关键成功包括PARP抑制剂olaparib，该药物在BRCA试验中可延长无进展生存期突变的乳腺癌，并且即将获得临床批准（在这种情况下）。然而，TNBC的异质性限制了“未选”患者中许多试验疗法的临床益处。此外，由于补偿性信号传导途径的上调，在使用许多靶向的单药治疗后，药物耐药性逐渐增强。在这篇综述中，我们评估了靶向治疗的当前状态，并提供了新颖的生物标志物和联合疗法在提高缓解率和规避药物引起的耐药性中的作用的证据。此外，我们讨论了通过临床前和/或流行病学研究确定的转移性TNBC中有希望的新型靶标。