Overcoming Trastuzumab-Pertuzumab Resistance and Optimizing Sequential Anti-HER2 Therapy in HER2-Positive Metastatic Breast Cancer - PubMed
7 hours ago
- #targeted therapy
- #drug resistance
- #breast cancer
- HER2-positive breast cancer comprises 15-20% of all breast cancers, with resistance to trastuzumab-pertuzumab in metastatic disease posing a major challenge.
- Resistance mechanisms include structural changes in HER2 (e.g., p95HER2, mutations), PI3K-AKT-mTOR pathway activation, bypass signaling via HER3/IGF-1R, immune evasion, and metabolic reprogramming.
- Sequential therapy with agents like trastuzumab deruxtecan (effective against heterogeneity/downstream activation) and tucatinib (for brain metastases/p95HER2) is crucial after first-line treatment.
- Future directions involve novel antibody-drug conjugates and bispecific antibodies to tailor therapy against complex resistance patterns.