克服乳腺癌内分泌耐药的靶向治疗新进展

Advances in targeted therapy for overcoming endocrine therapy resistance in breast cancer

内分泌治疗是激素受体阳性乳腺癌最有效的治疗方式,然而其有效性通常受到耐药的制约,这在进展期乳腺癌患者中几乎是不可避免的。最近,有许多研究对这些耐药模式的分子机制进行了探索,但仍未阐明其确切的机制,不过许多研究都将雌激素受体和生长因子受体信号通路之间的相互作用视为雌激素依赖性乳腺癌内分泌耐药的关键点。一些研究还探讨了介导内分泌耐药的不同分子途径,并对一些治疗靶点进行了评估。尽管大多数信号通路靶向制剂都还处于Ⅰ期或小范围Ⅱ期临床试验阶段,但一些研究已取得令人鼓舞的结果。本文旨在对乳腺癌内分泌治疗耐药的新进展进行综述。

Endocrine therapy is the most effective systemic treatment for patients with HR＋ （hormone-receptor-positive） breast cancer. Unfortunately, its efficacy is often limited by the onset of resistance, which is almost inevitable for patients with advanced disease. Current insights into the molecular basis for these resistance patterns are rudimentary. Although the underlying mechanism is still poorly clarified, many studies considered the ＂cross-talk＂ between ER （estrogen receptor） and growth factor receptor signaling pathways as the key in the development of estrogen-independent endocrine- resistant breast cancer. Several studies have provided current understanding of various endocrine resistance-related molecular pathways which were evaluated as therapeutic targets for ER-positive breast cancer. While most of the agents that target these pathways have only been tested in phaseⅠ or small phase Ⅱ clinical trials, some have shown encouraging results. The purpose of this review is to summarize the recent new progress in overcoming resistance to endocrine therapy in breast cancer.