# RET

Source: https://onco.cc/targets/ret/  
OnCo record `ret` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: driver; kinase
- Symbol: RET
- Class: kinase
- Biology: RET is the receptor tyrosine kinase for GDNF-family ligands.
- Where found: Medullary thyroid cancer; Papillary thyroid cancer; NSCLC; Colorectal cancer: gene fusion (ncoa4-ret, ccdc6-ret) 0.1%; Non-small-cell lung cancer: rearrangement, commonly kif5b-ret or ccdc6-ret 1-2%

## Notes

- Colorectal cancer: RET fusions (NCOA4-RET, CCDC6-RET) in about 0.1% of tumours (cBioPortal), again clustered in the wild-type, mismatch repair deficient, right-sided corner. Selpercatinib's approval for RET fusion-positive solid tumours is tumour-agnostic; the colorectal evidence is a handful of patients.
- Lung cancer: rearranged in 1 to 2% of adenocarcinomas, with KIF5B the dominant partner and CCDC6 second (cBioPortal), the reverse of thyroid cancer. Like the other fusions it needs an assay that reads rearrangements rather than exons.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/RET_proto-oncogene
- Wikipedia: https://en.wikipedia.org/wiki/RET_proto-oncogene

## Connected records

- biomarkers: [RET fusion and RET mutation](https://onco.cc/biomarkers/ret-fusion/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)](https://onco.cc/cancers/hereditary-ppgl/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Medullary thyroid cancer](https://onco.cc/cancers/medullary-thyroid-cancer/), [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://onco.cc/cancers/multiple-endocrine-neoplasia/), [Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)](https://onco.cc/cancers/men2-syndrome/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pheochromocytoma and paraganglioma (PPGL)](https://onco.cc/cancers/pheochromocytoma-paraganglioma/), [RET fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ret-fusion-nsclc/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- drugs: [AL2846](https://onco.cc/drugs/al2846/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [EP0031](https://onco.cc/drugs/ep0031/), [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Oncomine Dx Target Test](https://onco.cc/drugs/oncomine-dx-target-test/), [Pralsetinib](https://onco.cc/drugs/pralsetinib/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Selpercatinib](https://onco.cc/drugs/selpercatinib/), [Vandetanib](https://onco.cc/drugs/vandetanib/)
- companies: [Imagene AI](https://onco.cc/companies/imagene-ai/), [Lucence](https://onco.cc/companies/lucence/)
- pathways: [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Thyroid cancer (KEGG map)](https://onco.cc/pathways/thyroid-cancer-signalling/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- trials: [A Study of HS-10365 in Patients With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer](https://onco.cc/trials/nct06147570/), [ARROW (thyroid cohorts)](https://onco.cc/trials/arrow-thyroid/), [LIBRETTO-431](https://onco.cc/trials/libretto-431/), [LIBRETTO-531](https://onco.cc/trials/libretto-531/), [SELECT](https://onco.cc/trials/select-lenvatinib/)
- pairings: [Sequence: targeted therapy before immunotherapy in driver-positive NSCLC](https://onco.cc/pairings/targeted-before-io-nsclc/)
- key papers: [Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/), [Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/), [NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/), [Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies](https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [Thyroglobulin, calcitonin and CEA in thyroid cancer follow-up](https://onco.cc/technologies/thyroid-cancer-markers/)
- people: [Alexander Drilon](https://onco.cc/people/alexander-drilon/), [Justin F. Gainor](https://onco.cc/people/justin-gainor/), [Koichi Goto](https://onco.cc/people/goto-koichi/), [Lori J. Wirth](https://onco.cc/people/lori-wirth/), [Takashi Kohno](https://onco.cc/people/kohno-takashi/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- ideas: [A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling](https://onco.cc/ideas/idea-tr1-tumour-agnostic-approval-standard/), [Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review](https://onco.cc/ideas/idea-reg-tumour-agnostic-reliance/), [Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators](https://onco.cc/ideas/idea-moon-reciprocal-tumour-agnostic-approvals/)
- institutions: [Kyushu University Hospital](https://onco.cc/institutions/kyushu-university-hospital/), [National Cancer Center Hospital East](https://onco.cc/institutions/ncc-hospital-east/), [nationales Netzwerk Genomische Medizin Lungenkrebs](https://onco.cc/institutions/nngm/), [Shanghai Chest Hospital](https://onco.cc/institutions/shanghai-chest-hospital/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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JSON: https://onco.cc/api/v1/entities/ret.json