Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Nat Commun. 2022 Mar 18;13(1):1473. doi: 10.1038/s41467-022-29081-2.
Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16 is deficient in the majority of HER2+ BCBMs. p16-deficiency as measured by protein immunohistochemistry predicted response to combined tucatinib and abemaciclib in orthotopic patient-derived xenografts (PDXs) of HER2 + BCBMs. Our findings establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2 + BCBM.
约 50%的转移性人表皮生长因子受体 2 阳性（HER2+）乳腺癌患者会发生脑转移（BCBMs）。我们报告称，大多数 HER2+BCBMs 存在肿瘤抑制因子 p16 缺失。通过蛋白免疫组织化学检测到的 p16 缺失可预测曲妥珠单抗联合 abemaciclib 在 HER2+BCBM 原位患者来源异种移植（PDX）中的反应。我们的研究结果为针对 HER2+BCBM 患者进行联合 CDK4/6 和 HER2 靶向药物的生物标志物驱动的临床试验提供了依据。
