DLL3 expression

Our findings indicate that DLL3 is frequently expressed in MTC and its high expression identifies tumors with aggressive pathological characteristics and poor clinical outcomes. These results support DLL3 as a potential prognostic biomarker and therapeutic target in MTC, highlighting the need for further validation and integration into clinical trials of DLL3-directed therapies.

This multimodal profiling analysis provides further insights into the biologic complexity of SCLC and highlights potential therapeutic vulnerabilities of distinct disease subtypes.

Several radioligands have been developed by targeting DLL3 for immunoPET or radioimmunotherapy use. These ligands hold great promise for mapping the heterogeneous DLL3 expression in neuroendocrine tumors and guiding the DLL3-directed therapeutic strategies.

DLL3 is expressed on a majority of GEP NECs and on a subset of high-grade PanNETs marked by poor outcomes. Functional imaging suggests DLL3 as a promising therapeutic target in both GEP NECs and high-grade PanNETs.

Tarlatamab appeared effective when added to osimertinib. Further analysis of the combination of bispecific DLL3 T-cell engager and EGFR tyrosine kinase inhibitor is warranted to confirm these findings.

P1, N=18, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

In conclusion, integrating OTP and ASCL1 refines pulmonary NET classification into four histologically and biologically distinct subgroups, providing additional insight into tumor heterogeneity. O + /A + tumors showed solid-spindle features and diffuse GRP and frequent ACTH expression, trabecular patterns characterized ASCL1-negative tumors, while oncocytic histology predominated in OTP-negative tumors, highlighting their role in defining tumor heterogeneity.

P1, N=45, Active, not recruiting, Boehringer Ingelheim | Phase classification: P1/2 --> P1 | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2025

MK-6070 also demonstrates antitumor activity in mixed tumors, affecting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate the promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070.

MK-6070 also demonstrates anti-tumor activity in mixed tumors, impacting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070.

P1, N=300, Recruiting, Boehringer Ingelheim | Trial completion date: Dec 2025 --> Feb 2027 | Trial primary completion date: Sep 2025 --> Aug 2026

We describe the landscape of DLL3 and SEZ6 coexpression across NECs, establishing a broad-based cohort of patients who might derive benefit from therapeutics in development targeting these cell surface determinants.