Advancing Extrapulmonary NEC: DLL3 & Beyond

Are you treating extrapulmonary neuroendocrine carcinomas based on where they start—or what they actually are? In this faculty follow-up to their i3 Health activity (Clinical Challenges in Extrapulmonary NEC: Expert Insights on Diagnosis, Treatment, and Emerging Targets), Andrew Hendifar, MD, and Danielle Hutchings, MD (Cedars-Sinai Medical Center), unpack why treating these rare, aggressive tumors according to site of origin rather than tumor lineage can compromise outcomes. They clarify crucial pathologic distinctions between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) while emphasizing the essential role of multidisciplinary collaboration in precision care. The experts also explore the novel therapeutic landscape of delta-like ligand 3 (DLL3)–targeted therapies, highlighting the promise of DLL3 T-cell engagers in extrapulmonary disease. They address ongoing diagnostic hurdles—such as standardized immunohistochemistry (IHC) expression thresholds and expanding send-out testing access—while sharing key insights on emerging clinical trials evaluating T-cell engager monotherapies and chemo-immunotherapy combinations. Claim your CME credit: bit.ly/488fPhK Download and review the companion Clinical Challenges in Extrapulmonary NEC Slide Deck: bit.ly/4w2Pni3