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RET is a kinase altered in thyroid cancer and a small slice of lung cancer, treatable with one selective pill regardless of where the tumour is.
RET is the receptor tyrosine kinase for GDNF-family ligands, and cancers can switch it on either through gene fusions or point mutations. RET fusions occur in about 1 to 2 percent of NSCLC and in roughly 10 to 20 percent of papillary thyroid cancers, while RET mutations drive around 60 to 70 percent of medullary thyroid cancers. The selective inhibitors selpercatinib and pralsetinib produce responses in all of these settings, and selpercatinib holds a tumour-agnostic approval for RET-fusion solid tumours, with expanded labels in 2026. Selective inhibitors largely replaced older multikinase drugs such as vandetanib and cabozantinib because they are better tolerated. Acquired resistance through solvent-front mutations and the role of next-generation inhibitors are the open questions. For a newcomer: RET is a kinase treatable with one selective pill wherever the tumour is.
In plain words · RET is a kinase altered in thyroid cancer and a small slice of lung cancer, treatable with one selective pill regardless of where the tumour is.
RET is a kinase altered in thyroid cancer and a small slice of lung cancer, treatable with one selective pill regardless of where the tumour is.
RET is the receptor tyrosine kinase for GDNF-family ligands.
10 products aim at RET: small molecules and other agents. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (RET fusion and RET mutation) absent from normal cells. HPA RET: RNA tissue enhanced (adrenal gland 11 nTPM, parathyroid gland 19 nTPM); high antibody staining in 2 normal tissues; highest cancer staining melanoma (6 of 8 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Thyroid cancer, Lung cancer (all types)); Open Targets associates it with 17 specific cancer types at or above 0.5 (multiple endocrine neoplasia type 2A, medullary thyroid gland carcinoma, multiple endocrine neoplasia type 2B, pheochromocytoma, multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma and more). Tissue-agnostic: Selpercatinib US 2022: "RET-fusion solid tumours (tumour-agnostic)". (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: RET fusion and RET mutation label threshold; Human Protein Atlas RET tissue; Open Targets ENSG00000165731 associations
First described 1987. Earliest sequence paper UniProt cites for the protein: Takahashi et al, Mol. Cell. Biol, 1987, "ret transforming gene encodes a fusion protein homologous to tyrosine kinases". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
RET is the receptor tyrosine kinase for GDNF-family ligands.
RNA: tissue enhanced (adrenal gland 11 nTPM, parathyroid gland 19 nTPM), detected in many normal tissues.
Medium: Caudate, Cerebral cortex, Duodenum, Gallbladder, Hippocampus, Lung, Pancreas, Placenta.
RNA cancer enhanced: Breast Invasive Carcinoma 20 pTPM.
Medium only: breast cancer, carcinoid, endometrial cancer, head and neck cancer.
HPA RET tissue · HPA RET pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Thyroid cancer | 60-70% | RET mutation in medullary thyroid cancer | ~10-20% RET fusions in papillary | Wikipedia |
| Non-small-cell lung cancer | 1-2% | Fusion | cBioPortal (TCGA) | |
| Non-small-cell lung cancer | 1-2% | Rearrangement, commonly KIF5B-RET or CCDC6-RET | cBioPortal structural variants: 51 of 2,422, 2.1%, in luad_mskcc_2023_met_organotropism (KIF5B in 36 events, CCDC6 in 4); 38 of 2,621, 1.4%, in nsclc_ctdx_msk_2022; 16 of 915, 1.7%, in lung_msk_2017; 3 of 232, 1.3%, in lung_nci_2022. | cBioPortal (TCGA) |
| Colorectal cancer | 0.1% | Gene fusion (NCOA4-RET, CCDC6-RET) | cBioPortal structural variants: 8 of 7,237, 0.11% (NCOA4-RET 4), in crc_msk_2026; 1 of 1,134 in crc_msk_2017; CCDC6-RET in 1 of 594 in coadread_tcga_pan_can_atlas_2018; 1 of 1,516 in crc_eo_2020. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AL2846 is an experimental small-molecule drug from Chia Tai Tianqing Pharmaceutical in phase 3 trials for thyroid cancer, aimed at MET and RET.
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
EP0031 is an experimental small-molecule drug from Ellipses Pharma in phase 2 trials for non-small-cell lung cancer, aimed at RET.
A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs.
An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.
The first FDA-approved gene panel that could match one biopsy to several different lung cancer drugs at once.
Pralsetinib is the second selective RET pill for lung cancer, less used than selpercatinib after a change of owner and label.
A sorafenib successor that became the first second-line drug proven to prolong life in liver cancer (2017).
Selpercatinib is a selective RET inhibitor approved for any tumour with a RET fusion, with a further label update in July 2026.
Vandetanib was the first drug approved for medullary thyroid cancer (2011), now largely replaced by RET-selective selpercatinib.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
It showed the benefit of plasma testing is not only analytical but logistical: it reaches patients who are too unwell, or whose disease is too inaccessible, for a repeat biopsy.
It is the evidence behind running plasma and tissue together at diagnosis rather than in sequence, and the 80% sensitivity figure is the reason a negative plasma result never ends the work-up.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
It is the honest accounting of precision oncology in the disease where it works best: broad sequencing changes treatment for about one patient in three, and the bottleneck is evidence rather than detection.
Query for this target: (TITLE:"RET" OR ABSTRACT:"RET") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about RET, not a curated reading list.
Shares Koichi Goto, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Alexander Drilon, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer and the tags driver, kinase.
Shares Justin F. Gainor, Imagene AI, Lucence, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC and the tags driver, kinase.
Shares Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators, Imagene AI, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling and the tags driver, kinase.
Shares Imagene AI, Lucence, Vandetanib, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC and the tags driver, kinase.
Shares AL2846, Regorafenib, Lenvatinib, Receptor tyrosine kinase activation and the tags driver, kinase.
Shares Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, Gene fusion, Lenvatinib, Receptor tyrosine kinase activation and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.
Shares Receptor tyrosine kinase activation, Small-molecule kinase inhibitors, Colorectal cancer, Non-small-cell lung cancer and the tags driver, kinase.