2024 World Conference on Lung Cancer (WCLC) - Posters-P3.02G.04 JP11646-mediated PIM2 Inhibition Has Potent Antitumor Effects in Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma of the Lung

P3.02G.04 JP11646-mediated PIM2 Inhibition Has Potent Antitumor Effects in Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma of the Lung

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The study investigates the potential antitumor effects of the compound JP11646 on small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung. Both cancers are characterized by aggressive behavior and resistance to chemotherapy upon relapse. Key molecular mechanisms driving these cancers involve the MYC gene, which is stabilized by the PIM2 kinase, suggesting these pathways as potential targets for therapeutic interventions.<br /><br />JP11646 is a novel inhibitor of the PIM2 kinase, noted for its role in upregulating MYC activity, thereby contributing to cancer cell survival and proliferation. The study demonstrates that JP11646 significantly reduces cell viability in SCLC and LCNEC cell lines in vitro. A marked decrease in PIM2 and MYC-paralog protein expressions was observed upon treatment with JP11646, indicating its effectiveness in targeting the MYC-dependent pathways that drive these cancers.<br /><br />The research involved cell viability assays across different cancer cell lines, analysis of protein and RNA expression levels for PIM2 and MYC, as well as RNA interference techniques to modulate gene expression. Findings highlight that JP11646 reduces not only PIM2 levels but also affects MYC-paralog and PIM3 RNA expressions, indicating a broader impact on molecular signaling pathways within the cells.<br /><br />Future directions aim to validate the mechanism of JP11646, examining whether it operates via kinase-dependent or independent pathways and its influence on post-translational modifications. The team plans further investigations with in vivo xenograft models and phosphoproteomics to understand JP11646’s functional impact and detailed signaling processes.<br /><br />The findings suggest JP11646 as a promising therapeutic candidate for treating relapsed SCLC and LCNEC, with potential applications to broader cancer types involving MYC and PIM2 pathways.

Asset Subtitle

Katherine Minton

Meta Tag

Speaker Katherine Minton

Topic Tumor Biology – Preclinical Biology

Keywords

JP11646

antitumor effects

small cell lung cancer

large cell neuroendocrine carcinoma

PIM2 kinase

MYC gene

cancer cell viability

therapeutic interventions

RNA interference

xenograft models