fig3

Figure 3. Intrinsic resistance to KRAS inhibition in PDAC driven by Hippo pathway inactivation and AP-1/YAP–TAZ transcriptional cooperation. Pharmacological inhibition of KRAS suppresses MAPK signaling and ERK-dependent AP-1 (FOS/JUN) activity. Inactivation of the Hippo pathway stabilizes and promotes nuclear accumulation of YAP/TAZ, enabling TEAD-dependent transcription and cooperation with AP-1 to sustain KRAS-independent transcriptional programs associated with therapy resistance. Created in BioRender. Giovannetti, E. (2026) https://BioRender.com/69l6sp4. PDAC: Pancreatic ductal adenocarcinoma; AP-1: activator protein 1; YAP: Yes-associated protein; TAZ: transcriptional co-activator with PDZ-binding motif; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; FOS: Fos proto-oncogene; JUN: Jun proto-oncogene; TEAD: TEA domain transcription factor; RAF: rapidly accelerated fibrosarcoma; MEK1/2: mitogen-activated protein kinase kinase 1/2.