Anti-HER2 therapy in metastatic breast cancer: many choices and future directions.
Anti-HER2 therapy in metastatic breast cancer: many choices and future directions.
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DOI：
10.1007/s10555-022-10021-x
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Tang SC
中科院分区：
文献类型：
--
作者：
Wynn CS;Tang SC
转移性 HER2+乳腺癌是一个不断扩大的药物开发和研究领域，仅 2020 年就有三种新药获得批准。虽然转移性 HER2 + 乳腺癌的一线治疗已十分成熟，但根据 DESTINY-Breast03 试验的结果，二线治疗的护理标准可能很快就会发生变化。在第三线设置中，有很多选项可供选择。选择三线治疗方案时要考虑的因素包括对曲妥珠单抗的耐药性、脑转移的存在和耐受性。这种情况下存在高耐药率，特别是由于 p95 的表达，p95 是 HER2 的截短形式，可组成性激活下游信号通路。由于 TKI 在脑转移瘤和表达 p95 的肿瘤中具有活性，我们建议采用基于酪氨酸激酶抑制剂 (TKI) 的治疗方案。尝试用 PI3K 抑制剂、mTOR 抑制剂和 CDK 4/6 抑制剂克服抗 HER2 疗法的耐药性是一个活跃的研究领域。未来，需要生物标志物来帮助预测患者可能从哪些治疗中受益最多。我们回顾了许多正在开发的新药，包括具有新颖作用机制的药物。
Metastatic HER2 + breast cancer is an expanding area of drug development and research, with three new drugs approved in 2020 alone. While first-line therapy is well-established for metastatic HER2 + breast cancer, the standard of care for second-line therapy will likely be changing soon based on the results of the DESTINY-Breast03 trial. In the third-line setting, many options are available. Considerations in choosing between regimens in the third-line include resistance to trastuzumab, the presence of brain metastases, and tolerability. High rates of resistance exist in this setting particularly due to expression of p95, a truncated form of HER2 that constitutively activates downstream signaling pathways. We suggest a tyrosine kinase inhibitor (TKI)-based regimen because of the activity of TKIs in brain metastases and in p95-expressing tumors. Attempts to overcome resistance to anti-HER2 therapies with PI3K inhibitors, mTOR inhibitors, and CDK 4/6 inhibitors are an active area of research. In the future, biomarkers are needed to help predict which therapies patients may benefit from the most. We review the many new drugs in development, including those with novel mechanisms of action.
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