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Target intelligence / Profile preview
RET Proto-oncogene Receptor Tyrosine Kinase (RET)
- Target
- RET
- Molecular classification
- Receptor, Receptor Tyrosine Kinase
01
Overview
The RET proto-oncogene encodes a receptor tyrosine kinase essential for neural crest-derived tissue development. It is activated by GDNF family ligands and GFRα co-receptors, leading to downstream signaling via RAS-MAPK/ERK and PI3K/AKT pathways. Mutations or rearrangements in RET are implicated in Hirschsprung's disease (loss-of-function) and various cancers (gain-of-function), including MEN2 and MTC. RET is a therapeutic target, and selective RET inhibitors are being developed for cancer treatment.
- Other names
- MEN2AMEN2BMTC1PTC2CDHF12RET51RET43RET9
02
Mechanism of action
Small-molecule inhibitors that bind to and inhibit the RET kinase domain, preventing autophosphorylation and downstream signaling.
03
Biological functions
Signal transductionCell proliferationCell survivalCell differentiationEmbryonic development (ENS, kidney)Neuron function
04
Disease associations
Hirschsprung's diseaseMultiple endocrine neoplasia type 2A (MEN2A)Multiple endocrine neoplasia type 2B (MEN2B)Medullary thyroid carcinoma (MTC)PheochromocytomaParathyroid hyperplasiaPapillary thyroid carcinomaNon-small cell lung cancerColorectal cancerBreast cancerSalivary gland cancers
05
Safety considerations
Off-target effects of multikinase inhibitorsDevelopment of resistance to RET inhibitorsSpecific toxicities associated with individual inhibitors (e.g., hypertension, QT prolongation)Drug-drug interactions
06
Interacting drugs
Sorafenib
3 more in the full profile.
07
Biomarkers
RET mutations (e.g., M918T, C634R) in MEN2 and MTCRET fusions in NSCLC and other cancersRET protein expression levels
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