Fig. 1: Schematic diagram showing the mechanism of osimertinib resistance driven by the EGFR C797S mutation.

The schematic illustrates the mechanism of epidermal growth factor receptor (EGFR) C797S mutation-driven osimertinib resistance due to the increase in pyruvate dehydrogenase kinase (PDK)1 expression through the EGFR/Serine/Threonine Kinase 1 (AKT)/hypoxia-inducible factor (HIF)-1α axis; the combination of osimertinib with a PDK inhibitor can overcome this resistance.