p16<sup>INK4A</sup>-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35304445.
- Also identified by DOI 10.1038/s41467-022-29081-2 and PMC identifier 8933392.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16<sup>INK4A</sup> is deficient in the majority of HER2+ BCBMs. p16<sup>INK4A</sup>-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.
Medical subject headings
- Antineoplastic Agents
- Brain Neoplasms
- Breast Neoplasms