HER2 aberrations in cancer: implications for therapy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Anti-HER2 therapy is established for HER2-positive breast, gastric, and gastroesophageal cancers.
• HER2 aberrations, including gene amplification, mutations, and overexpression, are present in numerous other tumor types.

Observation:

• HER2 aberrations are found in 1-37% of bladder, cervix, colon, endometrium, germ cell, glioblastoma, head and neck, liver, lung, ovarian, pancreas, and salivary duct cancers.
• Approved HER2-targeted therapies for breast cancer include antibodies (trastuzumab, pertuzumab), an antibody-drug conjugate (ado-trastuzumab emtansine), and kinase inhibitors (lapatinib).
• Afatinib, a kinase inhibitor targeting EGFR and HER2, is approved for EGFR-mutated non-small cell lung cancer.

Findings:

• A significant number of diverse malignancies exhibit HER2 aberrations, suggesting broader therapeutic potential.
• Multiple HER2-targeted agents are in clinical development, indicating an expanding therapeutic landscape.

Implications:

• Understanding and targeting HER2 in various cancer types holds promise for new treatment strategies.
• The prevalence of HER2 aberrations across different tumors necessitates further investigation into targeted therapies beyond current approvals.