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Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Novel therapeutic approaches in GEP-NETs based on genetic and epigenetic alterations
Javier Pozas1, Teresa Alonso-Gordoa1, Maria San Román1
1Medical Oncology Department, Hospital Universitario Ramón y Cajal, Medicine School, Alcalá University, Madrid, Spain.
Abstract:
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies with distinct prognosis based on primary tumor localization, grade, stage and functionality. Surgery remains the only curative option in localized tumors, but systemic therapy is the mainstay of treatment for patients with advanced disease. For decades, the therapeutic landscape of GEP-NETs was limited to chemotherapy regimens with low response rates. The arrival of novel agents such as somatostatin analogues, peptide receptor radionuclide therapy, tyrosine kinase inhibitors or mTOR-targeted drugs, has changed the therapeutic paradigm of GEP-NETs. However, the efficacy of these agents is limited in time and there is scarce knowledge of optimal treatment sequencing. In recent years, massive parallel sequencing techniques have started to unravel the genomic intricacies of these tumors, allowing us to better understand the mechanisms of resistance to current treatments and to develop new targeted agents that will hopefully start an era for personalized treatment in NETs. In this review we aim to summarize the most relevant genomic aberrations and signaling pathways underlying GEP-NET tumorigenesis and potential therapeutic strategies derived from them.
Insights
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are complex cancers. Genomic insights are paving the way for personalized treatments beyond current therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are diverse malignancies with variable prognoses.
- Current treatments for advanced GEP-NETs, including chemotherapy and novel agents, have limitations in efficacy and sequencing.
- Understanding the genomic landscape is crucial for advancing GEP-NET treatment.
Purpose of the Study:
- To review key genomic aberrations and signaling pathways in GEP-NET tumorigenesis.
- To explore potential targeted therapeutic strategies based on these genomic findings.
- To highlight the shift towards personalized medicine in GEP-NET treatment.
Main Methods:
- Comprehensive literature review of genomic studies in GEP-NETs.
- Analysis of signaling pathways implicated in GEP-NET development and progression.
- Evaluation of emerging targeted therapies and their potential clinical application.
Main Results:
- Massive parallel sequencing is revealing the genomic complexity of GEP-NETs.
- Specific genomic alterations and activated pathways are identified as drivers of tumorigenesis.
- These findings offer insights into mechanisms of treatment resistance.
Conclusions:
- Genomic understanding is transforming GEP-NET treatment paradigms.
- Targeted agents based on specific molecular profiles hold promise for personalized therapy.
- Further research into optimal treatment sequencing and novel drug development is warranted.
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