2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - Posters-PP01.15: Antitumor activities of HER2- and TROP2-directed antibody drug conjugates in recalcitrant pulmonary high-grade neuroendocrine carcinomas

PP01.15: Antitumor activities of HER2- and TROP2-directed antibody drug conjugates in recalcitrant pulmonary high-grade neuroendocrine carcinomas

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The study investigates the expression of ERBB2 (HER2) and TACSTD2 (TROP2) across different subtypes of high-grade neuroendocrine carcinomas (hgNECs) of the lung, focusing on small cell lung cancer (SCLC). Both treatment-naïve and relapsed SCLC tumors exhibit various levels of these markers. Particularly, neuroendocrine and DLL3-low SCLC tumors with SCLC-P subtype show enriched HER2 and TROP2, making them potentially susceptible to targeted therapies.<br /><br />Two antibody-drug conjugates (ADCs), trastuzumab deruxtecan (HER2-ADC) and sacituzumab govitecan (TROP2-ADC), demonstrated significant in vitro and in vivo activity against these tumors. Sensitivity to these ADCs correlated with SLFN11, TOP1, and replication stress levels, suggesting these could be biomarkers for response prediction. The research indicates that HER2 and TROP2 ADCs can serve as effective treatments, especially in subtypes resistant to conventional therapies.<br /><br />The study emphasizes the potential of ADCs in targeting cell surface proteins in SCLC, providing a promising direction for treating resistant neuroendocrine tumors. Moreover, ERBB2 and TACSTD2 levels remain constant or rise in relapsed tumors, underscoring their role as stable therapeutic targets. Furthermore, disruption of these tumor markers via methylation also appears significant, as it affects gene expression.<br /><br />Acknowledgements note the substantial support from various NIH/NCI grants and other funding entities, underscoring the collaboration and resources leveraged to conduct this research. The study offers a compelling case for further clinical exploration of ADCs for lung cancers with specific molecular profiles.

Asset Subtitle

Kavya Ramkumar

Keywords

ERBB2

TACSTD2

high-grade neuroendocrine carcinomas

small cell lung cancer

antibody-drug conjugates

trastuzumab deruxtecan

sacituzumab govitecan

biomarkers

targeted therapies

molecular profiles