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Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors
Kristen McClellan1, Emerson Y Chen2, Adel Kardosh2
1School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Abstract:
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of malignancies originating from neuroendocrine cells of the gastrointestinal tract, the incidence of which has been increasing for several decades. While there has been significant progress in the development of therapeutic options for patients with advanced or metastatic disease, these remain limited both in quantity and durability of benefit. This review examines the latest research elucidating the mechanisms of both up-front resistance and the eventual development of resistance to the primary systemic therapeutic options including somatostatin analogues, peptide receptor radionuclide therapy with lutetium Lu 177 dotatate, everolimus, sunitinib, and temozolomide-based chemotherapy. Further, potential strategies for overcoming these mechanisms of resistance are reviewed in addition to a comprehensive review of ongoing and planned clinical trials addressing this important challenge.
Insights
This review explores resistance mechanisms to gastroenteropancreatic neuroendocrine tumor (GEP-NET) treatments. It also discusses strategies to overcome resistance and reviews ongoing clinical trials for advanced GEP-NETs.
Area of Science:
- Oncology
- Gastroenterology
- Medical Research
Background:
- Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly diagnosed malignancies.
- Current treatments for advanced or metastatic GEP-NETs offer limited durability of benefit.
- Understanding resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To review the latest research on resistance mechanisms to GEP-NET therapies.
- To explore strategies for overcoming treatment resistance.
- To provide a comprehensive overview of ongoing and planned clinical trials.
Main Methods:
- Literature review of recent studies on GEP-NET treatment resistance.
- Analysis of mechanisms underlying resistance to somatostatin analogues, peptide receptor radionuclide therapy (PRRT) with lutetium Lu 177 dotatate, everolimus, sunitinib, and temozolomide.
- Compilation of data on current and future clinical trials.
Main Results:
- Identified key mechanisms of both upfront and acquired resistance to major GEP-NET therapies.
- Highlighted potential therapeutic strategies to circumvent these resistance pathways.
- Summarized the landscape of ongoing and planned clinical investigations.
Conclusions:
- Resistance to GEP-NET therapies presents a significant clinical challenge.
- Targeting resistance mechanisms offers promising avenues for novel treatment strategies.
- Active clinical trials are essential for advancing the management of advanced GEP-NETs.
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