Figure 1.

An overview of oncogenic KRAS-driven RAF/MEK/ERK and PI3K/PDK1/AKT signalling networks in pancreatic cancer. Mutationally activated oncogenic KRAS engages the PI3K-PDK1-AKT pathway to drive cancer initiation, progression and maintenance. Additionally, activated KRAS signals through the canonical mitogen-activated protein kinase pathway via RAF-MEK1/2-ERK1/2. KRAS activity is enhanced by positive feedback activation of the epidermal growth factor receptor (EGFR) and possibly by other receptor tyrosine kinases (RTKs) that are engaged by autocrine and paracrine stimuli. Negative feedback loops and inhibitory as well as activating cross-signalling exist at various levels. Activating pro-tumourigenic signalling connections are depicted as arrows in green; inhibitory anti-tumourigenic pathways are shown as solid lines headed by a vertical line in red. Arrows in red depict activating anti-tumourigenic feedback loops. The asterisk (KRAS*) represents the mutational activation of KRAS.