Mechanisms Underlying Metabolic Adaptation in Osimertinib-Resistant H1975 Cells

Elucidate the precise molecular and biochemical mechanisms that drive the metabolic adaptations observed in osimertinib-resistant H1975 non-small cell lung cancer cells, including increased glycolysis, reduced oxidative pentose phosphate pathway activity, and activation of the pyruvate–acetaldehyde–acetate pathway.

Background

The authors integrate exometabolomic, transcriptomic, and proteomic data to describe a resistance-associated metabolic shift, noting enhanced glycolysis, suppressed oxidative PPP, mitochondrial dysfunction, and activation of a proposed PAA shunt.

Despite these observations, they explicitly acknowledge that the detailed mechanisms orchestrating these changes in osimertinib-resistant H1975 cells have not yet been fully delineated, indicating a need for deeper mechanistic studies.