Highlights
- Systematic identification of colon cancer-associated proteins and phosphosites
- Proteomics-supported neoantigens and cancer/testis antigens in 78% of the tumors
- Rb phosphorylation is an oncogenic driver and a putative target in colon cancer
- Glycolysis inhibition may render MSI tumors more sensitive to checkpoint blockade
Introduction
Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth leading cause of cancer-related deaths (Arnold et al., 2017). Recent studies of the genomic, transcriptomic, and proteomic landscapes of human CRC have identified many genomic alterations and have revealed extensive molecular heterogeneity of the disease (Cancer Genome Atlas Network, 2012, Guinney et al., 2015, Zhang et al., 2014).
However, the rapidly accumulating omics data have yet to bring novel biomarkers and drug targets to the clinic.Global proteomic differences between tumor and normal tissues, which are critical for cancer biomarker discovery, have not been systematically characterized in large tumor cohorts. Signaling proteins and pathways are often attractive therapeutic targets for cancer treatment, yet global phosphoproteomic analyses on human CRC are lacking.
Recent advances in cancer immunotherapy underscore the critical need for biomarkers to predict response to immune checkpoint inhibition and to select neoantigens for personalized vaccine development (Sharma et al., 2017). Proteogenomics can provide fresh approaches to these needs.
Here, we describe a proteogenomic study from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) on a prospectively collected colon cancer cohort to systematically identify new therapeutic opportunities.