Conclusions:

• We have identified and shortlisted several novel candidates that are enriched in a particular cancer indication using RNA-expression and protein localization by IHC on patient tissue. These targets were stratified into surface or intracellular targets based on their detection by cell-surface proteomics, ICC and flow cytometry.
• Caris cell surfaceome provides a strong foundation for discovery of novel surface targets exploiting three mass spectrometry approaches from >100 cancer cell lines and providing peptide level data focusing on ECD and transmembrane domain for the identification of novel cell surface targets that covers an array of indications.
• Our approach identifies modality-agnostic targets directly from patient tissue that are validated for presence, localization, protein expression, and dependency. Clinically actionable targets are evaluated to provide informed strategies for drug development across therapeutic modalities from biologics to small molecules.