2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03I.14 Osalmid Inhibits the Progression of Lung Adenocarcinoma and Sensitizes It to EGFR-TKIs: A Preclinical and Translational Study

P3.03I.14 Osalmid Inhibits the Progression of Lung Adenocarcinoma and Sensitizes It to EGFR-TKIs: A Preclinical and Translational Study

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This study explores the potential of osalmid, a novel RRM2 inhibitor, in treating lung adenocarcinoma (LUAD) and enhancing the efficacy of third-generation EGFR-TKIs for patients with EGFR mutations. Therapeutic resistance remains a significant challenge, necessitating new treatment approaches. The research analyzed patient survival data concerning RRM2 expression and conducted various in vitro and in vivo experiments to evaluate the effects of osalmid, AST2818, and AZD9291 as standalone therapies and in combination.<br /><br />Key findings revealed that patients with higher RRM2 expression had worse survival outcomes, suggesting that RRM2 plays a crucial role in LUAD progression and could be a therapeutic target. Osalmid treatment, particularly when combined with AST2818, significantly decreased the proliferation and colony formation of LUAD cell lines. This combination was shown to lower the IC50 values of AST2818 and AZD9291, indicating enhanced efficacy. The combination index (CI) values suggested a strong synergistic effect between osalmid and AST2818.<br /><br />Additionally, the study indicated that prolonged AST2818 treatment could upregulate RRM2 expression, implying a possible mechanism of resistance to AST2818 that osalmid could potentially overcome. The combination therapy showed a higher tumor suppression rate (89%) compared to single treatments (70%). <br /><br />These findings suggest that osalmid not only inhibits LUAD progression but also increases its sensitivity to EGFR-TKIs by targeting RRM2, offering promising translational implications for the development of clinical trials aimed at improving treatment outcomes for LUAD patients.

Asset Subtitle

Lei-Lei Wu

Meta Tag

Speaker Lei-Lei Wu

Topic Tumor Biology – Translational Biology

Keywords

osalmid

RRM2 inhibitor

lung adenocarcinoma

EGFR-TKIs

therapeutic resistance

patient survival

synergistic effect

tumor suppression

combination therapy

translational implications