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Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Profiling mTOR pathway in neuroendocrine tumors.
S Cingarlini1, M Bonomi, V Corbo
1Section of Medical Oncology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy. sara.cingarlini@ospedaleuniverona.it
Targeted Oncology
|August 15, 2012
Summary
The mammalian target of rapamycin (mTOR) pathway is activated in neuroendocrine tumors (NETs), driving tumor growth. mTOR inhibitors, like Everolimus, are now approved for advanced NETs, offering a new treatment paradigm.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The mammalian target of rapamycin (mTOR) pathway regulates cell growth, proliferation, and protein synthesis.
- Neuroendocrine tumors (NETs) have shown activation of the mTOR pathway, with upstream regulators PTEN and TSC2 frequently mutated in sporadic pancreatic NETs (pNETs).
- MicroRNA-21 (miR-21) overexpression in aggressive NETs further contributes to mTOR activation by targeting PTEN.
Purpose of the Study:
- To review the involvement of the mTOR pathway in NETs.
- To discuss the clinical evidence supporting mTOR inhibitors in cancer treatment.
- To identify current clinical challenges in managing NETs with mTOR inhibitors.
Main Methods:
- Analysis of gene and protein expression profiles in NETs.
- Global microRNA expression analysis.
- Review of clinical trial data for mTOR inhibitors in NETs.
Main Results:
- mTOR pathway activation is confirmed in both experimental and human sporadic NETs.
- Downregulation of TSC2 and altered PTEN expression are observed in well-differentiated NETs.
- miR-21 overexpression correlates with aggressive tumor behavior and mTOR activation.
Conclusions:
- The findings provide a strong rationale for using mTOR inhibitors in treating pNETs.
- Everolimus, an mTOR-targeted drug, has been approved for advanced pNETs, marking a clinical translation.
- Further research is needed to optimize patient management and address remaining clinical issues.
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