Resistance mechanisms and prospects of trastuzumab

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• HER2-positive breast cancer accounts for 15-20% of all breast cancer cases.
• Trastuzumab is a standard first-line therapy for HER2-positive advanced breast cancer.
• Over 50% of patients exhibit primary or acquired resistance to trastuzumab.

Purpose of the Study:

• To review current research on trastuzumab resistance mechanisms in HER2-positive breast cancer.
• To elucidate resistance mechanisms from genetic, molecular, signaling pathway, and tumor microenvironment perspectives.
• To outline emerging research and novel therapeutic strategies for overcoming trastuzumab resistance.

Main Methods:

• Literature review of existing research on trastuzumab resistance.
• Analysis of resistance mechanisms targeting HER2, including genetic loci, molecular structure, signaling pathways, and the tumor microenvironment.
• Synthesis of current research progress and identification of new therapeutic avenues.

Main Results:

• Resistance mechanisms are multifaceted, involving genetic alterations, HER2 pathway reactivation, and tumor microenvironment modulation.
• Understanding these mechanisms is crucial for predicting treatment response and developing alternative therapies.
• Several novel strategies are under investigation to overcome trastuzumab resistance.

Conclusions:

• Trastuzumab resistance is a significant clinical challenge in HER2-positive breast cancer management.
• A comprehensive understanding of resistance mechanisms is essential for advancing treatment efficacy.
• Future research should focus on developing targeted therapies and combination strategies to overcome resistance and improve patient outcomes.