Proteomic landscape of pan-tissue neuroendocrine carcinomas defines subtype-specific functional architectures, biomarkers and therapeutic targets.

Proteomic analysis of 267 neuroendocrine carcinomas reveals five subtypes with distinct molecular and therapeutic vulnerabilities, including NAD+ dependency in subtype H.

• Why it matters: Neuroendocrine carcinomas are highly diverse and lethal, with limited targeted treatments, highlighting the need for a detailed molecular understanding to improve clinical outcomes.
• What they did: The study conducted comprehensive proteomic and phosphoproteomic profiling across multiple tissue sites, identifying subtype-specific transcription factors, biomarkers, and metabolic dependencies, especially NAD+ vulnerability in subtype H.
• The result: Findings enable precise classification and targeted therapy development, exemplified by NAMPT inhibition inducing tumor regression, and identify immune microenvironment subtypes that predict immunotherapy response, advancing personalized NEC treatment.