SEZ6 (Seizure Related 6 Homolog)

As a result of this SCLC-like to LCNEC-like evolution, YAP1 -positive cells lack several clinically relevant SCLC surface targets (i.e., DLL3, SEZ6), but are enriched for others (i.e., B7-H3, TROP2). We propose a model where YAP1 expressing cells emerge with SCLC treatment resistance and characterize a tenacious subpopulation capable of diverging from the treatment naïve lineage and adopting features to evade therapeutic response.

ADCs are transforming lung cancer therapy by delivering potent cytotoxics with manageable safety. Next-generation bispecific and biparatopic formats may broaden eligibility, improve tumor penetration, and delay resistance. Incorporating predictive biomarkers and real-time monitoring will be key to their use in earlier disease and to establishing ADCs as a cornerstone of precision oncology.

P1, N=288, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

While ADCs have generated encouraging response rates in SCLC, durability has remained limited. Future development will require optimization of payloads, linkers, and trial design to determine whether ADCs can achieve a sustained role in this disease.

Molecular docking studies explored the interactions of these CRGs with entinostat. In conclusion, SEZ6, S100B, SPIB, and TFF1 were identified as significant prognostic genes in BRCA, providing insights into BRCA pathogenesis and potential personalized treatment strategies.

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.

SEZ6 has emerged as a novel target for antibody-drug conjugate (ADC) therapy, and early studies have shown promising antitumor activity, demonstrating the potential for SEZ6 to be targeted by drugs with alternate mechanisms of action. Here, we review the current knowledge of the biology of SEZ6 and its implications in malignancy, summarize the preclinical and clinical findings of SEZ6 targeted ADCs, and discuss future directions to further elucidate the role of SEZ6 in SCLC and other neuroendocrine neoplasms.

For decades, outcomes stagnated: most patients present with extensive-stage disease, screening rarely detects early tumors, surgery is seldom feasible, and platinum-etoposide remained the first-line standard with median overall survival (OS) 80% of SCLC, enables T-cell-redirecting therapy: the bispecific T-cell engager tarlatamab improved OS to 13.6 vs 8.3 months over standard second-line chemotherapy, with manageable cytokine release syndrome and occasional ICANS. B7 homolog 3 (B7-H3, CD276), uniformly expressed across SCLC subtypes and linked to poor prognosis, is another compelling target: the antibody-drug conjugate ifinatamab deruxtecan achieved a 54.8% response rate and meaningful survival in heavily pretreated patients, earning FDA Breakthrough designation. Together, DLL3- and B7-H3-directed therapies (with additional ADCs against Trop-2 and SEZ6 in development) are redefining second-line and later care. Key next steps include optimizing sequencing/combination strategies, managing BiTE-specific toxicities, and developing predictive biomarkers. After decades of futility, SCLC is transitioning from uniform chemotherapy to a precision-medicine paradigm with cautious optimism.

P1, N=350, Recruiting, AbbVie | Trial completion date: Nov 2027 --> Jun 2026 | Trial primary completion date: Nov 2027 --> Jun 2026

The knockdown of IGF2BP2 also confined the tumor growth in vivo. In the present study, IGF2BP2 promotes the progression of DDP-resistant NSCLC by mediating m6A methylation on SEZ6L2 mRNA, providing a certain reference for the treatment of DDP-resistant NSCLC.

Expression appears to be limited primarily to NENs and is rarely seen only focally and weakly in non-NENs. The presence of one or both of these antigens offers a novel approach to the treatment of patients with neuroendocrine neoplasms across the entire spectrum.

B7-H3 showed consistent, high expression across SCLC molecular subtypes, whereas DLL3 and SEZ6 expression varied significantly. These data suggest B7-H3-targeting ADCs may be active across SCLC subtypes, consistent with the high reported response rates.