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Clinical and Preclinical Advances in Gastroenteropancreatic Neuroendocrine Tumor Therapy
1Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Abstract:
The molecular events leading to gastroenteropancreatic neuroendocrine tumor (GEP-NET) formation are largely unknown. Over the past decades, systemic chemotherapies have been replaced by therapies directed at particular molecular targets such as the somatostatin receptors, mTOR complexes or proangiogenic molecules. These approaches have demonstrated some success in subtypes of this heterogeneous tumor group, but responses are still widely varied. This review highlights the clinical trials ongoing for neuroendocrine tumors (NETs) and includes emerging immunotherapy, which holds great promise for NETs based on successes in other tumor types. Current avenues of preclinical research, including Notch and PI3K/AKT, will lead to additional targeted therapies based on genome-wide studies that have cast a wide net in the search for driver mutations. Future preclinical and clinical investigations are required to identify those mutations predictive of therapeutic response or disease progression. Results of current clinical trials outlined here will better inform patient management with respect to agent selection, timing, duration and combination therapy in the treatment of NETs.
Insights
Molecular events driving gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remain unclear. This review covers ongoing clinical trials, emerging immunotherapies, and preclinical research for GEP-NETs, aiming to improve targeted treatment selection and patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Translational Medicine
Background:
- Gastroenteropancreatic neuroendocrine tumor (GEP-NET) development mechanisms are poorly understood.
- Traditional chemotherapy is being superseded by targeted therapies (somatostatin receptors, mTOR, proangiogenic molecules) with variable efficacy.
- Heterogeneity within GEP-NETs contributes to diverse treatment responses.
Purpose of the Study:
- To review current clinical trials for neuroendocrine tumors (NETs).
- To explore emerging immunotherapies and preclinical research avenues (Notch, PI3K/AKT) for NETs.
- To identify future research needs for predicting therapeutic response and disease progression.
Main Methods:
- Literature review of ongoing clinical trials in neuroendocrine tumors.
- Analysis of emerging immunotherapy data and preclinical research findings.
- Synthesis of information from genome-wide studies to identify potential driver mutations.
Main Results:
- Current targeted therapies show varied success in different NET subtypes.
- Immunotherapy presents significant promise for NET treatment, mirroring successes in other cancers.
- Preclinical research is exploring novel targets like Notch and PI3K/AKT pathways.
Conclusions:
- Further preclinical and clinical studies are essential to identify predictive biomarkers for NET treatment response.
- Understanding molecular drivers is crucial for developing more effective, personalized therapies for GEP-NETs.
- This review provides insights into ongoing trials to guide future patient management strategies, including agent selection and combination therapies.
