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RET inhibition: implications in cancer therapy
Maria Grazia Borrello1, Elena Ardini, Laura D Locati
1UO Molecular Mechanisms, Experimental Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via GA. Amadeo, 42-20133 Milano, Italy. mariagrazia.borrello@istitutotumori.mi.it
Expert Opinion on Therapeutic Targets
|March 7, 2013
Summary
The RET gene is crucial for development and implicated in various cancers, including thyroid and lung. Current RET-targeting drugs show limited efficacy and significant side effects, highlighting the need for improved therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The RET gene encodes a receptor tyrosine kinase vital for nervous system and kidney development.
- RET rearrangements (RET/PTC) are common in papillary thyroid carcinoma.
- Activating RET mutations drive hereditary syndromes like MEN2A/MEN2B and FMTC.
Purpose of the Study:
- To review the role of the RET gene and protein in cancer.
- To discuss RET as a therapeutic target.
- To evaluate current preclinical and clinical studies on RET-targeted therapies.
Main Methods:
- Literature review of RET gene involvement in cancer.
- Analysis of preclinical and clinical studies on RET-targeted agents.
- Discussion of multitargeted inhibitors and their efficacy.
Main Results:
- RET rearrangements are found in a subset of lung adenocarcinomas.
- Multitargeted inhibitors targeting VEGFR/PDGFR have been studied in thyroid cancer.
- These inhibitors show limited duration of action and significant side effects.
Conclusions:
- Current RET-targeting therapies, particularly in thyroid cancer, have limitations.
- There is a critical need for more specific and effective RET-targeting drugs.
- Further research is required to develop improved therapeutic strategies for RET-driven cancers.
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