Predictive Biomarkers of Antibody–Drug Conjugate Efficacy for Solid Tumors: Current Challenges and the Potential Role of Quantitative Proteomics

Antibody-drug conjugate (ADC) development is progressing rapidly, with significant impacts on the treatment landscape of clinical oncology. However, the development of predictive biomarkers to guide ADC selection has not kept pace and to date has been mostly limited to immunohistochemistry, hampering patient selection and personalized treatment recommendations. Here, we review the current state of ADC target protein assessment and the association between target expression levels and therapeutic efficacy. We discuss the limitations and challenges of existing protein assessment technology and highlight the potential clinical role of quantitative mass spectrometry-based proteomics for rapid, comprehensive, and accurate protein quantification. We propose that integrating multiplexed proteomic assays early in ADC development and clinical trial design can improve therapeutic targeting, enhance clinical trial design, and ultimately lead to more personalized ADC-based treatment strategies.