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Updated: Dec 18, 2025
Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Using genetics to inform the pharmacological targeting of neuroendocrine neoplasms
Ashley K Clift1,2, Andrea Frilling1
1Department of Surgery and Cancer, Imperial College London, London, UK.
Abstract:
Neuroendocrine neoplasms (NEN) are a class of tumours heterogeneous in terms of their anatomical sites of origin and clinical behaviour. Outdated perspectives of indolence have been superseded by appreciation for their myriad clinical challenges, such as the high rates of regional and distant metastases at initial diagnosis, lack of clarity on optimal treatment strategies/sequencing, and incompletely elucidated genetic/other pathophysiological drivers. The first randomised controlled trials in this arena were published approximately a decade ago - since then, increased understanding of the genetic drivers and signalling pathway perturbations in these tumours have suggested promise for precision therapy influenced by an individual tumour's molecular sub-type, but this is yet to be realised for manifold reasons. In this article, the authors review the genetic landscapes as currently understood for selected forms of NEN and discuss the current and developing evidence to support the use of genetic information to influence therapy. They provide a critical assessment of the potential limitations of using such approaches and also posit avenues for future developments in this arena.
Insights
Neuroendocrine neoplasms (NENs) present complex challenges due to metastasis and unclear treatments. Understanding NEN genetic landscapes offers potential for precision therapies, though challenges remain in clinical application.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Neuroendocrine neoplasms (NENs) are diverse tumors with challenging clinical behaviors.
- High rates of metastasis at diagnosis and unclear treatment strategies complicate patient management.
- Limited understanding of genetic drivers and pathophysiological mechanisms hinders optimal care.
Purpose of the Study:
- To review the current understanding of genetic landscapes in selected NENs.
- To discuss evidence supporting the use of genetic information in guiding NEN therapy.
- To critically assess limitations and future directions for precision medicine in NENs.
Main Methods:
- Literature review of genetic landscapes in NENs.
- Analysis of current and developing evidence for genetic-guided therapy.
- Critical assessment of limitations and future research avenues.
Main Results:
- Genetic landscapes of selected NENs are increasingly understood.
- Growing evidence supports tailoring therapy based on molecular subtypes.
- Significant challenges persist in realizing precision therapy due to various factors.
Conclusions:
- Understanding NEN genetic profiles is crucial for advancing treatment.
- Precision medicine approaches hold promise but require further development and validation.
- Future research should focus on overcoming barriers to clinical implementation of genetic information in NEN care.
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