Antibody-Drug Conjugates in Breast Cancer: What Is Beyond HER2?

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• The advent of antibody-drug conjugates (ADCs) has transformed breast cancer therapeutics, moving beyond human epidermal growth factor receptor 2 (HER2) targeting.
• Novel surface antigens with differential expression in tumors offer promising new targets for ADC development, expanding treatment options.

Approach:

• This review provides an overview of clinical trials investigating ADCs against novel antigens beyond HER2.
• It discusses essential target characteristics for ADC design and current challenges in biomarker assessment, patient selection, and treatment sequencing.

Key Points:

• Sacituzumab govitecan, targeting trophoblast cell surface antigen 2, is the sole non-HER2 ADC approved for breast cancer.
• Numerous ADCs targeting new antigens like HER3 and LIV-1 are in various developmental stages.

Conclusions:

• Exploring novel ADC targets is crucial for increasing the number of breast cancer patients who can benefit from this therapy.
• Future advancements require addressing challenges in biomarker assessment, patient selection, and optimizing ADC sequencing.