A promising discovery by scientists against lung cancer drug resistance
A promising discovery by scientists against lung cancer drug resistance
The resistance mechanism to osimertinib, a third-generation targeted therapy used in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC), has been uncovered by a team of Turkish researchers.
In a study published in Cell Death & Disease, scientists from the Izmir Biomedicine and Genome Center and Dokuz Eylul University identified the AP-1 transcription factor—particularly its subunits FOSL1 and JUN—as key drivers of acquired resistance in drug-insensitive cells. The study's co-first authors, Bengisu Dayanç and Sude Eriş, demonstrated through epigenetic and multi-omics analyses that AP-1 becomes activated in resistant cells, triggering the MEK/ERK signaling pathway, which enhances cell survival and promotes resistance to osimertinib. These findings were confirmed through CRISPR-based genetic screening.
Importantly, inhibiting AP-1—either genetically or pharmacologically—restored drug sensitivity and reversed resistance-related cellular changes, offering a promising strategy for overcoming resistance in advanced NSCLC cases.
Prof. Dr. Şerif Şentürk, who led the study, emphasized that the discovery lays important groundwork for developing new combination therapies for patients with osimertinib-resistant lung cancer.
Article link: https://www.nature.com/articles/s41419-025-07711-z