pertuzumab
Overview
Pertuzumab is a recombinant humanized monoclonal antibody that binds to the HER2 (ERBB2) dimerization domain (domain II), blocking HER2–HER3 heterodimerization and downstream PI3K/AKT and RAS/MAPK signaling. It is used in combination with trastuzumab for HER2-positive breast cancer.
Evidence in the corpus
- TCGA breast cancer study identified two subtypes of clinically HER2+ disease: HER2E mRNA subtype (strong HER1/p-HER1/HER2/p-HER2 RPPA signal) vs. Luminal mRNA subtype (higher ER/GATA3/BCL2 expression); these subtypes may respond differently to anti-HER2 therapies including pertuzumab; HER2E subtype shows co-activation of HER1/EGFR suggesting potential benefit from dual HER1/HER2 targeting PMID:23000897.
- ERBB2-altered CCA (4–6% iCCA, 3–20% eCCA): MyPathway phase IIa basket ORR 23% in combination with trastuzumab; ERBB2 overexpression is an independent poor-prognostic factor after curative resection PMID:25526346
Resistance mechanisms
- Two-class heterogeneity within clinically HER2+ breast cancer (HER2E vs. Luminal mRNA subtype) may influence response to pertuzumab; the ERBB2 TK domain mutations in lobular cancers may represent distinct resistance mechanisms PMID:23000897.
Cancer types (linked)
- BRCA — HER2-positive breast cancer; HER2E and Luminal mRNA subtypes within HER2+ disease may respond differently.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:25526346
This page was processed by crosslinker on 2026-05-14.