Cancer Center and Research Institute, University of Mississippi Medical Center, Guyton Research Building, G-651-07, 2500 North State Street, Jackson, MS, 39216, USA.
Cancer Metastasis Rev. 2022 Mar;41(1):193-209. doi: 10.1007/s10555-022-10021-x. Epub 2022 Feb 10.
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.
转移性 HER2+乳腺癌是药物开发和研究的一个不断扩大的领域，仅 2020 年就批准了三种新药。虽然转移性 HER2+乳腺癌的一线治疗已经确立，但基于 DESTINY-Breast03 试验的结果，二线治疗的标准护理可能很快就会改变。在三线治疗中，有许多选择。在三线治疗方案中选择方案时需要考虑的因素包括对曲妥珠单抗的耐药性、脑转移的存在和可耐受性。由于存在 p95，即 HER2 的截断形式，它会持续激活下游信号通路，因此该治疗环境中存在很高的耐药率。我们建议使用基于酪氨酸激酶抑制剂（TKI）的方案，因为 TKI 在脑转移和表达 p95 的肿瘤中具有活性。尝试使用 PI3K 抑制剂、mTOR 抑制剂和 CDK4/6 抑制剂来克服抗 HER2 治疗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哪些疗法对患者最有效。我们回顾了许多正在开发中的新药，包括具有新型作用机制的药物。
Zotero 插件
