Figure 1.

Co-expression of 2 potent oncogenes in the same cell may result in different outcomes. Expression of 2 strong oncogenes (KRAS and BRAF; or KRAS and EGFR) hyperactivates their downstream signaling pathways (ERK, AKT, mTOR etc.), and leads to transcriptional activation of target proteins. The most frequently reported suit of proteins encompasses cyclin-dependent kinase inhibitors, p15^Ink4b,p16^Ink4a, and p19^Arf. Those proteins may, in turn, drive cells toward senescence, or death through either apoptosis, or the recently described form of cell death, methuosis. In our recent paper²² we suggest that induction of senescence underlies the mutual exclusivity of KRAS^G12D and BRAF^V600E in lung cancer.