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. This dossier gathers the 6 products (6 approved), 17 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
RET is the receptor tyrosine kinase for GDNF-family ligands.
- Medullary thyroid cancer
- Papillary thyroid cancer
- NSCLC
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| 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) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| M918T 918 | Activating | not sourced | The MEN2B germline allele and the most common somatic mutation in sporadic medullary thyroid cancer; highly sensitive to selpercatinib. | — | COSMIC: RET | |
| C634R and other cysteine codons 634 | Activating | not sourced | MEN2A germline hotspot in the cysteine-rich domain; forms constitutive dimers. | — | COSMIC: RET | |
| V804M / V804L (gatekeeper) 804 | Resistance | not sourced | Blocks vandetanib and cabozantinib; selpercatinib and pralsetinib were designed to tolerate it. | Solomon et al., J Thorac Oncol 2020 | ||
| G810R/S/C (solvent front) 810 | Resistance | not sourced | Acquired after selpercatinib or pralsetinib; next-generation RET inhibitors are designed around it. | none in corpus | Solomon et al., J Thorac Oncol 2020 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: RET.
Products by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Small molecule 6 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
| LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| CABINET (Alliance A021602) NCT03375320 | 3 | Positive | Previously treated advanced pancreatic (n=95) and extra-pancreatic (n=203) NETs: cabozantinib vs placebo | PFS HR 0.23 (pNET), 0.38 (epNET). | |
| LEAP-012 NCT04246177 | 3 | Mixed | Unresectable non-metastatic HCC: TACE + lenvatinib + pembrolizumab vs TACE + placebo | PFS HR 0.66; final OS HR 0.98. | |
| CONTACT-03 NCT04338269 | 3 | Negative | Advanced RCC progressing on or after a PD-1/PD-L1 inhibitor: atezolizumab + cabozantinib vs cabozantinib | PFS HR 1.03; OS HR 0.94, negative. | |
| LIBRETTO-431 NCT04194944 | 3 | Positive | First-line RET-fusion advanced NSCLC: selpercatinib vs platinum-pemetrexed ± pembrolizumab | PFS HR 0.46. | |
| LIBRETTO-531 NCT04211337 | 3 | Positive | Untreated progressive RET-mutant medullary thyroid cancer: selpercatinib vs cabozantinib or vandetanib | PFS HR 0.28; 12-month PFS 86.8% vs 65.7%. | |
| COSMIC-313 NCT03937219 | 3 | Mixed | Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab | PFS HR 0.73; OS HR 1.02 (no benefit). | |
| LEAP-002 NCT03713593 | 3 | Negative | First-line unresectable HCC: lenvatinib + pembrolizumab vs lenvatinib | OS HR 0.84, not significant. | |
| CLEAR (KEYNOTE-581) NCT02811861 | 3 | Positive | Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm) | PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79. | |
| KEYNOTE-775 / Study 309 NCT03517449 | 3 | Positive | Advanced endometrial cancer after platinum: lenvatinib + pembrolizumab vs doxorubicin or weekly paclitaxel | OS 18.3 vs 11.4 months (HR 0.62). | |
| CheckMate 9ER NCT03141177 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + cabozantinib vs sunitinib | PFS HR 0.51; OS HR 0.77 at ~4 years (46.5 vs 36.0 months). | |
| CELESTIAL NCT01908426 | 3 | Positive | HCC after sorafenib (up to two prior lines): cabozantinib vs placebo | OS 10.2 vs 8.0 months, HR 0.76. | |
| REFLECT NCT01761266 | 3 | Positive | First-line unresectable HCC: lenvatinib vs sorafenib (non-inferiority) | OS 13.6 vs 12.3 months, non-inferior (HR 0.92). | |
| RESORCE NCT01774344 | 3 | Positive | HCC progressing on sorafenib: regorafenib vs placebo | OS 10.6 vs 7.8 months, HR 0.63. | |
| SELECT NCT01321554 | 3 | Positive | Radioiodine-refractory differentiated thyroid cancer with progression: lenvatinib vs placebo | PFS 18.3 vs 3.6 months; HR 0.21. | |
| ARROW (thyroid cohorts) NCT03037385 | 1/2 | Positive | RET-mutant medullary and RET-fusion thyroid cancer: pralsetinib | ORR 71% (naive MTC), 89% (RET-fusion thyroid). |
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →No pathway diagram carries this target as a node.
Companion diagnostics and assays
Assay registry →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| FoundationOne Liquid CDx Foundation Medicine (Roche) · FDA CDx 2020 | NGS plasma | Per companion claim: EGFR (osimertinib, erlotinib, gefitinib), ALK (alectinib), BRCA1/2 and ATM (olaparib, rucaparib), PIK3CA (alpelisib), FGFR3 (erdafitinib), NTRK and RET; negative plasma results reflex to tissue | |
| Oncomine Dx Target Test Thermo Fisher Scientific · FDA CDx 2017 | NGS tissue | Per companion claim: BRAF V600E (dabrafenib plus trametinib), ROS1 fusions (crizotinib), EGFR (gefitinib), RET fusions (pralsetinib), MET exon 14 (tepotinib), EGFR exon 20 insertions |
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →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.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/ret.json. Licence CC BY 4.0.