@article{TLCR120036,
author = {Leilei Wu and Zhijian Xu and Wenmei Jiang and Shangshang Ma and Diego Gonzalez-Rivas and Weiliang Zhu and Dong Xie},
title = {Osalmid inhibits lung adenocarcinoma progression and enhances EGFR-TKI responses: a preclinical and translational study},
journal = {Translational Lung Cancer Research},
volume = {15},
number = {6},
year = {2026},
keywords = {},
abstract = {Background: Therapeutic resistance to current treatment strategies indicates the need for more effective agents to treat lung adenocarcinoma (LUAD). RRM2 dysregulation has been implicated in LUAD progression and therapeutic resistance. However, whether pharmacological inhibition of ribonucleotide reductase regulatory subunit M2 (RRM2) by osalmid may suppress LUAD growth and enhance epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) responses remains unclear. We sought to explore the antitumor effects of osalmid and investigate potential combinatorial approaches with third-generation EGFR-TKIs to treat LUAD patients with EGFR mutations.Methods: Patient data were used to analyze survival based on RRM2 expression. In vitro and in vivo experiments explored the antitumor effects of AZD9291 (Osimertinib), osalmid, and AST2818 (Alflutinib) as single agents and in combination. The combination index (CI) was conducted to assess the synergy effect of two drugs. Ferroptosis-related data obtained via CRISPR screens and western blotting were used to explore the relationships between RRM2 and ferroptosis suppressor genes (GPX4 and SLC7A11). Immunohistochemical analysis of 4-hydroxynonenal (4-HNE) was conducted to evaluate lipid peroxidation in tumor tissues after treatment with osalmid.Results: Patients with high RRM2 expression had poorer survival than patients with low RRM2 expression (P},
issn = {2226-4477}, url = {https://tlcr.amegroups.org/article/view/120036}
}