KRAS signaling is associated with the disease progression in various cancers such as colorectal, pancreatic and lung. KRAS is a proto-oncogene which encodes a small GTPase transductor protein and its mutation occurs in up to 25% of all human tumors. KRAS mutant has been considered undruggable for the last three decades and tumor stratification appears to be crucial to therapeutic success due to the heterogeneous nature of KRAS-driven tumors.
BRAF mutations have been reported in melanoma (50-60%), colorectal (10%), thyroid (30-50%) cancers with majority being V600E mutation occurring in about 8% of human tumors. This mutation stimulates ERK signaling, proliferation and transformation
EGFR is another most frequently altered oncogenes in cancers, with two types of pathological alterations, kinase-activating mutation and over-expression of the EGFR protein)
APC mutations are found in colon (80%), pancreatic and gastric cancers. Co-mutation of BRAF and APC has been reportedly associated with aggressive neoplastic phenotype and poor patient outcome.