Internal tumor heterogeneity presents enormous challenges to achieve complete therapeutic responses. Although tumor heterogeneity has been thoroughly investigated at the genomic and transcriptomic levels, limited studies have investigated heterogeneity at the proteomic level. Changes in protein expression are central determinants of cancer phenotypes, as they integrate the genetic and the environmental signals and reflect the cellular function and therapeutic targets. Through multi-region proteomic analysis of tumor samples and single cell proteomic approaches we determine the proteomic heterogeneity, and associate the proteomic profiles with patient clinical parameters. Generation of the comprehensive proteomic tumor maps serves as the basis for development of novel cancer therapeutics.
Tumors present high internal heterogeneity, due to clonal evolution and due to the interaction with the tumor microenvironment. Proteomics of distinct regions identifies the extent of heterogeneity and the proteomic distance between adjacent regions.