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Target intelligence / Profile preview
Rearranged during Transfection Proto-Oncogene Receptor Tyrosine Kinase (RET)
- Target
- RET
- Molecular classification
- Receptor, Receptor tyrosine kinase, Proto-oncogene
01
Overview
The Rearranged during Transfection (RET) proto-oncogene encodes a receptor tyrosine kinase that is essential for the normal development and maturation of various tissues. Aberrant activation or mutation/fusion events involving *RET* can drive oncogenesis in several cancers, including thyroid cancer and lung cancer. RET is activated by GDNF family ligands through GFRα co-receptors, leading to receptor dimerization and autophosphorylation. Activated RET triggers downstream signaling pathways such as MAPK, PI3K/AKT, and JAK/STAT. Therapeutic targeting of RET with selective inhibitors like pralsetinib and selpercatinib has shown significant efficacy in *RET*-driven cancers.
- Other names
- RET proto-oncogeneRET receptor tyrosine kinase
02
Mechanism of action
Tyrosine kinase inhibition
03
Biological functions
Embryonic kidney developmentEnteric nervous system developmentNeural crest cell migrationCell proliferationCell survivalCell differentiationSignal transductionHomeostasis
04
Disease associations
Hirschsprung’s diseasePapillary thyroid carcinomaMultiple endocrine neoplasiaPheochromocytomaParathyroid hyperplasiaNon-small cell lung cancerCancer
05
Safety considerations
Toxicities associated with multi-targeted TKIs (e.g., cabozantinib, vandetanib)Potential for off-target effects with less selective inhibitors
06
Interacting drugs
Cabozantinib
3 more in the full profile.
07
Biomarkers
RET fusions (e.g., KIF5B-RET, CCDC6-RET)RET mutations (e.g., MEN2A/2B mutations)
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