Systemic therapeutic strategies for GEP-NETS: what can we expect in the future?

Area of Science:

• Oncology
• Molecular Biology
• Translational Medicine

Background:

• Significant progress in understanding neuroendocrine tumor (NET) molecular biology, including angiogenesis and the PI3K-AKT-mTOR pathway.
• Identification of key transcription factors (e.g., DDIT3, ZNF274, ATM) in pancreatic NET pathogenesis.
• Emerging therapeutic agents show promise but face challenges with low remission rates and survival impact.

Purpose of the Study:

• To review recent advancements in biomarker and new agent development for neuroendocrine tumor (NET) treatment.
• To highlight the need for improved patient stratification and biomarker incorporation in NET management.
• To discuss strategies for understanding and overcoming therapeutic resistance in NETs.

Main Methods:

• Comprehensive review of current literature on NET molecular biology, biomarkers, and therapeutic agents.
• Analysis of data regarding angiogenesis and PI3K-AKT-mTOR pathway involvement in NETs.
• Evaluation of emerging transcription factors and their relevance in NET pathogenesis.

Main Results:

• NET pathogenesis involves critical roles for angiogenesis and the PI3K-AKT-mTOR pathway.
• Specific transcription factors are implicated in pancreatic NETs.
• Despite new agents, objective remission rates and survival benefits remain limited.
• Biomarker identification is crucial for patient selection and treatment optimization.

Conclusions:

• Integrating biomarkers into NET management is essential for personalized therapy.
• Understanding and addressing mechanisms of resistance is critical for improving treatment efficacy.
• Combination strategies and sequential therapies hold promise for overcoming treatment escape.
• Careful management of toxicities associated with targeted agents and combinations is necessary.