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Association details:
| Biomarker: | HER-2 V777L + PIK3CA H1047R |
|---|---|
| Cancer: | Breast Cancer |
| Drug: | Nerlynx (neratinib) (EGFR inhibitor, HER2 inhibitor, HER4 inhibitor) + Enhertu (fam-trastuzumab deruxtecan-nxki) (Topoisomerase I inhibitor, HER2-targeted antibody-drug conjugate) |
| Direction: | Sensitive |
Evidence:
Title:
Breast cancer mutations HER2V777L and PIK3CAH1047R activate the p21-CDK4/6 –Cyclin D1 axis driving tumorigenesis and drug resistance
Published date:
11/10/2022
Excerpt:
To study the effects of co-occurring HER2 and PIK3CA mutations, we bred genetically engineered mice with the HER2V777L; PIK3CAH1047Rtransgenes (HP mice) and studied the resulting breast cancers both in vivo as well as ex vivo...HP breast cancers have resistance to the pan-HER tyrosine kinase inhibitor, neratinib, but are effectively treated by neratinib plus trastuzumab deruxtecan....Combining neratinib with CDK4/6 inhibitors was another effective strategy for HP breast cancers with neratinib plus palbociclib showing a statistically significant reduction in mouse HP tumors as compared to either drug alone.
DOI:
https://doi.org/10.1101/2022.11.09.515796
