Epidermal growth factor receptor mutations in breast Cancer: Therapeutic challenges and way forward

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) frequently upregulated in aggressive triple-negative breast cancer (TNBC).
• EGFR activation by ligands regulates key cancer cell processes including growth, proliferation, migration, and survival.
• EGFR inhibition has demonstrated potential in modulating chemosensitivity in breast cancer stem cells.

Purpose of the Study:

• To review therapeutic strategies targeting EGFR in breast cancer.
• To discuss challenges associated with EGFR mutations and resistance to current therapies.
• To propose the development of next-generation inhibitors for combinatorial approaches.

Main Methods:

• Literature review of therapeutic approaches targeting EGFR.
• Analysis of resistance mechanisms, including EGFR mutations.
• Exploration of combinatorial therapies involving EGFR inhibitors.

Main Results:

• Clinically approved EGFR inhibitors (TKIs and mAbs) exist for breast cancer treatment.
• Intrinsic and acquired resistance due to EGFR mutations limits the efficacy of current EGFR-TKIs.
• Combinatorial therapy with chemo- or immune therapeutics is suggested to overcome resistance.

Conclusions:

• Targeting EGFR is a validated strategy in breast cancer, particularly TNBC.
• EGFR mutations present a significant challenge, necessitating novel therapeutic approaches.
• Development of advanced EGFR inhibitors for combination therapies is essential for improving treatment outcomes and preventing relapse.