Antibody-Drug Conjugates and Beyond: Next-Generation Targeted Therapies for Breast Cancer

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Breast cancer is a leading cause of cancer-related death globally.
• Antibody-drug conjugates (ADCs) offer targeted therapy by linking antibodies to cytotoxic drugs.
• Existing ADCs primarily target HER2 (human epidermal growth factor receptor 2), with significant clinical success.

Purpose of the Study:

• To review recent advancements in ADCs for breast cancer treatment.
• To highlight next-generation ADCs beyond HER2-targeting agents.
• To discuss mechanistic, technological, and clinical developments in ADC therapy.

Main Methods:

• Systematic literature review of ADCs in breast cancer.
• Analysis of ADC structural components (antibody, linker, payload).
• Integration of preclinical findings and clinical evidence for various breast cancer subtypes.

Main Results:

• ADCs like trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) significantly improve progression-free and overall survival.
• ADCs demonstrate efficacy in HER2-positive, HER2-low, and triple-negative breast cancer (TNBC).
• Emerging ADCs target HER3 (human epidermal growth factor receptor 3) and Nectin-4, alongside bispecific and immune-stimulatory approaches.

Conclusions:

• ADCs represent a paradigm shift in precision oncology for breast cancer.
• Novel ADC designs and targets offer improved outcomes by overcoming resistance and reducing toxicity.
• Future opportunities lie in engineering more selective and effective ADC platforms for diverse breast cancer subtypes.