Related Experiment Video
Updated: May 3, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinically actionable genomic and transcriptomic landscape of advanced neuroendocrine neoplasms
Simon Kreutzfeldt1, Leonidas Apostolidis2, Małgorzata Oleś3
1Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg, Germany.
Background:
Epithelial neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of malignancies with limited treatment options. Comprehensive molecular characterization may reveal novel therapeutic opportunities for these clinically challenging tumors.
Methods:
Within a nationwide precision oncology program, we performed whole-genome/exome and transcriptome sequencing in 168 patients with a diagnosis of advanced NEN from diverse anatomic origins, followed by evaluation of real-world outcomes associated with molecularly guided interventions.
Findings:
Our analysis revealed substantial molecular heterogeneity across advanced NENs, including distinct genetic profiles between low-grade and high-grade tumors, as well as alterations specific to particular tissues of origin. Candidate therapeutic targets included elevated tumor mutational burden induced by temozolomide exposure, rare actionable kinase mutations, overexpression of targetable antigens, and signatures of homologous recombination deficiency, providing a rationale for immune checkpoint blockade, kinase inhibitors, antibody-drug conjugates, poly(ADP-ribose) polymerase (PARP) inhibitors, and platinum-based therapies, respectively. Overall, 144 patients (85.7%) received molecularly guided treatment recommendations, of which 85 were implemented in 57 patients (39.6%). Among 68 evaluable therapy outcomes, 47 (69.1%) demonstrated clinical benefit (objective response, n = 25; disease stabilization, n = 22). At the patient level, 34 of the 57 treated (59.6%) experienced clinical benefit from at least one therapy (objective response, n = 18; disease stabilization, n = 16).
Conclusions:
Comprehensive genomic and transcriptomic profiling identified distinct molecular alteration patterns and therapeutic vulnerabilities among different classes of epithelial NENs from various tissues, warranting further investigation in anatomic-site-specific studies. Our outcome data underscore the clinical utility of broad molecular profiling in patients with advanced NENs lacking further standard treatment options.
Funding:
Funding for the study was institutional.
Insights
Comprehensive molecular profiling of advanced neuroendocrine neoplasms (NENs) reveals significant heterogeneity and identifies actionable therapeutic targets. Molecularly guided treatments show promising clinical benefit in patients with these rare cancers.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Epithelial neuroendocrine neoplasms (NENs) are rare, heterogeneous malignancies with limited treatment options.
- Comprehensive molecular characterization is crucial for identifying novel therapeutic strategies.
Purpose of the Study:
- To perform whole-genome/exome and transcriptome sequencing on advanced NENs.
- To evaluate real-world outcomes of molecularly guided interventions for NENs.
Main Methods:
- Nationwide precision oncology program.
- Sequencing of 168 advanced NEN patients.
- Analysis of molecular alterations and treatment outcomes.
Main Results:
- Identified substantial molecular heterogeneity in NENs, with distinct profiles based on grade and tissue of origin.
- Discovered candidate therapeutic targets including actionable mutations, antigen overexpression, and homologous recombination deficiency.
- Molecularly guided treatments demonstrated significant clinical benefit, with 69.1% objective response or disease stabilization in evaluable outcomes.
Conclusions:
- Genomic and transcriptomic profiling reveals distinct molecular patterns and vulnerabilities in epithelial NENs.
- Molecular profiling is clinically useful for advanced NENs lacking standard treatment options.
- Further site-specific studies are warranted.
More Related Videos
09:33Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
11:50Genome-Wide Mapping of Histone Modifications and Transcription Factor Binding Sites in Neuroendocrine Small Cell Lung Cancer Cell Lines Using CUT&RUN
Published on: April 3, 2026
