fig2

Figure 2. Schematic overview of KRAS signaling and its inhibitors in PDAC. KRAS, a GTPase, functions as a molecular switch between GDP- and GTP-bound states to drive RAF–MEK–ERK and PI3K–AKT–mTOR signaling, promoting cell proliferation and survival through transcriptional programs in the nucleus. The figure highlights inhibitors targeting the KRAS pathway at multiple levels, including upstream regulators, KRAS activation (ON and OFF states), its membrane localization, and downstream signaling effectors. Created in BioRender. Giovannetti, E. (2026) https://BioRender.com/u3f3uc9. PDAC: Pancreatic ductal adenocarcinoma; GDP: guanosine diphosphate; GTP: guanosine triphosphate; RAF: rapidly accelerated fibrosarcoma; MEK: mitogen-activated protein kinase kinase; ERK: extracellular signal-regulated kinase; PI3K: phosphoinositide 3-kinase; AKT: AKT serine/threonine kinase; mTOR: mechanistic target of rapamycin; GRB2: growth factor receptor-bound protein 2; SHP2: Src homology 2 domain-containing protein tyrosine phosphatase 2; SOS: son of sevenless; GAP: GTPase-activating protein; GEF: guanine nucleotide exchange factor; PLK1: Polo-like kinase 1.