Researchers reported multiple preclinical strategies that overcome lung‑cancer drug resistance, including novel combinations that target epigenetic regulators and metabolic adaptations. Studies demonstrated restored sensitivity to frontline agents in resistant models and identified candidate biomarkers for patient selection. In parallel, the histone demethylase inhibitor GSK‑J4 showed anti‑tumor activity in non‑small cell lung cancer cell models, supporting epigenetic targeting as a viable route to combat resistance. These programs may move toward early‑stage trials focused on molecularly defined resistant populations.