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Oral Sessions
Day 4, June 25（Wed.） 11:25-11:40
Room C (Top of Yaima)
- 4C-O1-1125
Clinical Functional Proteomics Applied to Pancreatic Cancer
(SUSTech)
oRuijun Tian
Spatial proteomics has drawn tremendous attention recently due to its powerfulness for unbiasedly discovering proteins with spatial resolution. Multidimensional integration with PTM and protein complex profiling makes it unique for systematically exploring functional proteome. By further taking advantage of the recent advances in biological mass spectrometry and integrated proteomics sample preparation, we developed the clinical functional proteomics strategy, termed TMEPro, and applied it to limited amount of pancreatic tumor cohort samples (Fig. 1). TMEPro allowed to explore the functional proteome which spatiotemporally regulates the intercellular signaling in the pancreatic tumor microenvironment (TME). In-depth bioinformatic analysis revealed the intercellular signaling loop between cancer cells and stromal cells and generic shedding of transmembrane receptors providing additional dimension of intercellular signaling regulation. Importantly, high-sensitive spatial glycoproteomics with absolute quantification demonstrated the potential of spatial proteomics for stratifying pancreatic cancer patients for the targeted therapy by the receptor tyrosine kinase AXL inhibitor R428. Last but not the least, pancreatic cancer organoid-based phenotypic validation revealed that combined treatment of R428 and a protease inhibitor rescuing MMP protease-based shedding has significant synergistic effect, indicating their potential for receiving better therapeutic benefit from R428 which entered in phase II clinical trial for pancreatic cancer.