Figure 1, Key Figure.

Determinants of Tumor Pathogenesis and Measures to Inform Precision Therapy

The genetic and phenotypic characteristics of a patient’s tumor are influenced by tissue/cell type specific factors, germline genetic background, lifestyle factors, as well as the number and type of previous anticancer drugs received [25, 27, 28]. Each individual cell is further influenced by, first, the proximity to and the integrity of the tumor vasculature; second, the biochemical and biophysical properties of the surrounding extracellular matrix (ECM); third, competing/cooperating interactions between individual tumor cells or tumor and stromal cells (among which are cancer associated fibroblaststs (CAFs), endothelial cells (ECs), and bone marrow-derived cells (BM-DCs)); and fourth, anti-tumor immunity. These factors further shape the geno- and phenotypic properties of a tumor in a spatial and temporal manner. While the genomic analysis of a tumor biopsy at the time of diagnosis identifies genetic vulnerabilities, the inclusion of transcriptomic data holds the additional potential of identifying non-genetic vulnerabilities by considering pathway activity and the composition of the tumor microenvironment. The integrated analysis of genomic and transcriptomic data is therefore a valuable tool to inform precision therapy.