2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.43 Overlap of DLL3 and SEZ6 Expression in High-Grade Neuroendocrine Carcinomas

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DLL3 and SEZ6 proteins are potential therapeutic targets in small cell lung cancer (SCLC) and other high-grade neuroendocrine carcinomas (HGNEC) due to their preferential expression on tumor cells. Tarlatamab, a DLL3-targeting therapy, has received FDA accelerated approval, and other therapies targeting DLL3 and SEZ6 are currently under development. While DLL3 inhibits notch signaling, facilitating neuroendocrine tumor growth, the role of SEZ6 in cancer development is not well understood. This study aims to explore the expression landscape of DLL3 and SEZ6 and their correlation with clinical outcomes.<br /><br />The study analyzed 124 patients with HGNEC, using staining tests to determine the expression of DLL3 and SEZ6 in tumors, defined as positive with at least 1% staining. The results revealed a frequent co-expression of DLL3 and SEZ6 in HGNEC across various tumor sites. Testing results were often at the extremes, showing either nearly full or no staining, with few intermediate values. Most patients maintained consistent expression over time; however, changes were observed in a few cases post-treatment.<br /><br />No clear association was found between the expression levels of DLL3 and SEZ6 and progression-free survival in patients with lung HGNEC treated with platinum/etoposide. Thus, further research is necessary to determine how the expression of these proteins impacts treatment outcomes and overall patient survival. Understanding this could potentially lead to better-targeted therapies in treating high-grade neuroendocrine carcinomas.

Asset Subtitle

Jessica Ross

Keywords

DLL3

SEZ6

small cell lung cancer

SCLC

high-grade neuroendocrine carcinomas

HGNEC

tarlatamab

therapeutic targets

notch signaling

protein expression