Triple-negative breast cancer (TNBC) shows a higher response rate to systemic therapy compared with other breast cancer subtypes. However, the tumor differentiation of TNBC is poorer, with an early tendency to metastasis and a higher recurrence rate. Relapsed and metastatic TNBCs usually progress more rapidly, showing strong resistance to chemotherapy and radiotherapy. Due to the lack of combinatorial targeted drugs, alternative treatments fail to improve these patient's prognosis and the quality of life. Finding the Achilles' heel of TNBC is critical for patients with advanced TNBC. Here, we summarize the latest advances in the mechanisms underlying TNBC therapeutic resistance, consider how these mechanisms may affect the development and utilization of TNBC targeted drugs, and discuss the rationale of relevant signals as therapeutic targets. Also, we review the clinical trials registered in ClinicalTrial.gov for TNBC patients, which comprehensively reveals current research and development of novel TNBC targeted drugs and future trends.

与其他乳腺癌亚型相比，三阴性乳腺癌（TNBC）对全身治疗的反应率更高。然而，TNBC的肿瘤分化较差，具有早期转移的趋势和较高的复发率。复发和转移性TNBC通常进展更快，显示出对化学疗法和放射疗法的强大抵抗力。由于缺乏组合靶向药物，替代疗法无法改善这些患者的预后和生活质量。找到TNBC的跟腱对于晚期TNBC患者至关重要。在这里，我们总结了TNBC治疗耐药性机制的最新进展，并考虑了这些机制如何影响TNBC靶向药物的开发和利用，并讨论相关信号作为治疗目标的理由。此外，我们还将回顾在ClinicalTrial.gov中为TNBC患者注册的临床试验，该试验全面揭示了针对TNBC的新型药物的当前研究与开发情况以及未来趋势。