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itraconazole + osimertinib

Development stage: Unknown
Lead developer: AstraZeneca
Modality: Small Molecules
Administration: Oral

Overview

A combination therapy consisting of itraconazole (an antifungal agent and CYP3A4 inhibitor) and osimertinib (a third-generation EGFR inhibitor). This combination has shown synergistic effects in overcoming acquired resistance to osimertinib in EGFR-mutant non-small cell lung cancer (NSCLC). Mechanistically, the combination promotes proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/DUSP13B/p-STAT3 and Hedgehog pathways, and suppression of c-Myc.

Brand names: TagrissoSporanox
Other names: AZD9291 + itraconazole

Targets

CYP3A4 (Cytochrome P450 3A4)Epidermal growth factor receptor (mutant)EGFR (Epidermal growth factor receptor)

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