Leveraging Quantitative Proteomics and Extracellular Vesicle Data to Uncover Druggable Receptor Kinases Across...

Extracellular vesicles (EVs) play an important role in cancer progression and metastasis. The increasing clinical proteomics data provides an opportunity to uncover new biomarkers and therapeutic targets in cancer specific EVs. Here, we present an integrated data analysis approach that leverages a comprehensive protein catalog from EVs, blood plasma, and the cancer cell surface to identify EV-associated proteins and evaluate their potential as therapeutic targets in cancer cells. Quantitative proteomics data from 12 cancer types (n = 2,272) identified 3,250 proteins that are commonly found in EV studies and EV quantity data. Receptor kinases (RKs) are crucial in cancer signalling pathways and have been widely studied targets. Our analysis focused on identifying RKs with significant high expression in cancer types that were also detected in EVs. Notably, PTK7 emerged as a significant target with high expression or survival association in seven independent cancer cohorts. We then explored the druggability of the RKs. Our analysis of drug repurposing network and RNAi screening suggested PTK7 as a potential therapeutic target with no FDA approved drugs in cancer. Overall, this integrative analysis proposes a framework to prioritize EV-associated candidates for downstream therapeutic investigation in cancer.