Medullary thyroid gland carcinoma

Summary

Medullary thyroid gland carcinoma (MONDO:0015277) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers; 8 ClinVar predisposition records) and 101 clinical trials. Molecularly, RET Mutation confers sensitivity to Selpercatinib in Medullary Thyroid Carcinoma (CIViC Level A); 17 further subtype–drug associations are mapped below. Top therapeutic interventions include cabozantinib, vandetanib, and selpercatinib.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 8
• Phenotypes (HPO): 14
• Clinical trials: 101
• Precision-medicine evidence (CIViC): 18 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.22	Europe	Validated
Point prevalence	1-9 / 100 000	5	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.17	United States	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0002865	Medullary thyroid carcinoma	Obligate (100%)
HP:0003528	Elevated calcitonin	Very frequent (80-99%)
HP:0005994	Nodular goiter	Very frequent (80-99%)
HP:0000975	Hyperhidrosis	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002716	Lymphadenopathy	Frequent (30-79%)
HP:0001618	Dysphonia	Occasional (5-29%)
HP:0001824	Weight loss	Occasional (5-29%)
HP:0002666	Pheochromocytoma	Occasional (5-29%)
HP:0008200	Primary hyperparathyroidism	Occasional (5-29%)
HP:0010622	Neoplasm of the skeletal system	Occasional (5-29%)
HP:0030146	Abnormal liver parenchyma morphology	Occasional (5-29%)
HP:0100526	Neoplasm of the lung	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	medullary thyroid gland carcinoma
Mondo ID	MONDO:0015277
Orphanet	1332
DOID	DOID:3973
ICD-11	578519098
NCIT	C3879
SNOMED CT	255032005
UMLS	C0238462
MedGen	66772
GARD	0007004
MedDRA	10027101
Is cancer (heuristic)	yes

Also known as: C cell carcinoma · carcinoma of parafollicular cell · carcinoma, C-cell, malignant · medullary carcinoma · medullary carcinoma of the thyroid · medullary carcinoma of the thyroid gland · medullary carcinoma of thyroid · medullary carcinoma of thyroid gland · medullary thyroid cancer · medullary thyroid cancer (MTC) · medullary thyroid carcinoma · medullary thyroid gland carcinoma · MTC · parafollicular cell carcinoma · THME · thyroid cancer, medullary · thyroid carcinoma, medullary · thyroid gland medullary cancer · thyroid gland medullary carcinoma · thyroid gland neuroendocrine carcinoma (+1 more)

Data availability: 8 ClinVar variants · 1 HPO phenotype · 16 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › neuroendocrine carcinoma › medullary thyroid gland carcinoma

Related subtypes (11): small cell carcinoma, anal canal neuroendocrine neoplasm, large cell neuroendocrine carcinoma, pancreatic endocrine carcinoma, combined lung carcinoma, malignant adrenal gland pheochromocytoma, liver neuroendocrine carcinoma, goblet cell carcinoma, cutaneous neuroendocrine carcinoma, thymic neuroendocrine carcinoma, vulvar neuroendocrine carcinoma

Subtypes (1): familial medullary thyroid carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523339	NM_001370259.2(MEN1):c.371_372del (p.Val124fs)	MEN1	Pathogenic	criteria provided, single submitter
13919	NM_020975.6(RET):c.2753T>C (p.Met918Thr)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13951	NM_020975.6(RET):c.2671T>G (p.Ser891Ala)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
24931	NM_020975.6(RET):c.1996A>G (p.Lys666Glu)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
24881	NM_020975.6(RET):c.961G>A (p.Gly321Arg)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
24883	NM_020975.6(RET):c.1531G>A (p.Glu511Lys)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
24943	NM_020975.6(RET):c.2452G>A (p.Glu818Lys)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
24960	NM_020975.6(RET):c.2656C>T (p.Arg886Trp)	RET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 17 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RET	Act	ANGS,MEL,NSCLC,PGNG,SOFT_TISSUE,WDTC	CIViC #42
MEN1	LoF	ACC,BLCA,BRCA,HCC,LUNG,PANCREAS,PANET,WDTC	CIViC #3485

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RET	Orphanet:146	Differentiated thyroid carcinoma
RET	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:247698	Multiple endocrine neoplasia type 2A
RET	Orphanet:247709	Multiple endocrine neoplasia type 2B
RET	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
RET	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
RET	Orphanet:388	Hirschsprung disease
RET	Orphanet:93100	Renal agenesis, unilateral
RET	Orphanet:99361	Isolated familial medullary thyroid carcinoma
RET	Orphanet:99803	Haddad syndrome
MEN1	Orphanet:2965	Prolactinoma
MEN1	Orphanet:314786	Silent pituitary adenoma
MEN1	Orphanet:314790	Null pituitary adenoma
MEN1	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:97279	Insulinoma
MEN1	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:99879	Familial isolated hyperparathyroidism

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	clinvar,civic_evidence
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
MEN1	Other/Unknown	no		Menin

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
granulocyte	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
RET	4,203

Intra-cohort edges

A	B	Sources
MEN1	RET	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
RET	P07949	34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the nephric duct	1	317.2×	0.028	RET
NPAS4 regulates expression of target genes	1	248.3×	0.028	RET
Formation of the ureteric bud	1	248.3×	0.028	RET
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	184.2×	0.028	MEN1
RHO GTPases activate IQGAPs	1	173.0×	0.028	MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	154.3×	0.028	MEN1
Formation of WDR5-containing histone-modifying complexes	1	132.8×	0.028	MEN1
RET signaling	1	129.8×	0.028	RET
Deactivation of the beta-catenin transactivating complex	1	116.5×	0.028	MEN1
Signaling by TGF-beta Receptor Complex	1	100.2×	0.029	MEN1
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.032	MEN1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.032	MEN1
Formation of the beta-catenin:TCF transactivating complex	1	60.1×	0.032	MEN1
TCF dependent signaling in response to WNT	1	58.9×	0.032	MEN1
Signaling by TGFB family members	1	57.7×	0.032	MEN1
Signaling by WNT	1	56.0×	0.032	MEN1
Post-translational protein phosphorylation	1	50.1×	0.034	MEN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.037	MEN1
Epigenetic regulation of gene expression	1	35.7×	0.042	MEN1
RHO GTPase Effectors	1	34.0×	0.042	MEN1
RAF/MAP kinase cascade	1	30.5×	0.045	RET
Signaling by Rho GTPases	1	17.1×	0.074	MEN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.074	MEN1
RNA Polymerase II Transcription	1	11.3×	0.105	MEN1
Post-translational protein modification	1	9.6×	0.118	MEN1
Gene expression (Transcription)	1	8.9×	0.122	MEN1
Generic Transcription Pathway	1	7.5×	0.138	MEN1
Metabolism of proteins	1	6.2×	0.161	MEN1
Signal Transduction	1	5.1×	0.187	MEN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
MAPK cascade	2	153.2×	0.002	RET, MEN1
embryonic epithelial tube formation	1	4213.0×	0.003	RET
posterior midgut development	1	4213.0×	0.003	RET
positive regulation of metanephric glomerulus development	1	2808.7×	0.003	RET
ureter maturation	1	2106.5×	0.003	RET
Peyer’s patch morphogenesis	1	2106.5×	0.003	RET
GDF15-GFRAL signaling pathway	1	2106.5×	0.003	RET
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	1053.2×	0.005	MEN1
T-helper 2 cell differentiation	1	936.2×	0.005	MEN1
lymphocyte migration into lymphoid organs	1	936.2×	0.005	RET
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	766.0×	0.006	RET
positive regulation of cell size	1	648.1×	0.006	RET
glial cell-derived neurotrophic factor receptor signaling pathway	1	601.9×	0.006	RET
membrane protein proteolysis	1	526.6×	0.006	RET
positive regulation of cell adhesion mediated by integrin	1	526.6×	0.006	RET
osteoblast development	1	495.6×	0.006	MEN1
neuron cell-cell adhesion	1	495.6×	0.006	RET
enteric nervous system development	1	495.6×	0.006	RET
response to pain	1	443.5×	0.006	RET
regulation of axonogenesis	1	443.5×	0.006	RET
neuron maturation	1	401.2×	0.006	RET
obsolete negative regulation of DNA-binding transcription factor activity	1	366.4×	0.006	MEN1
negative regulation of protein phosphorylation	1	290.6×	0.007	MEN1
response to gamma radiation	1	290.6×	0.007	MEN1
negative regulation of JNK cascade	1	280.9×	0.007	MEN1
positive regulation of transforming growth factor beta receptor signaling pathway	1	263.3×	0.007	MEN1
ureteric bud development	1	227.7×	0.008	RET
transcription initiation-coupled chromatin remodeling	1	191.5×	0.009	MEN1
response to UV	1	183.2×	0.010	MEN1
neural crest cell migration	1	168.5×	0.010	RET

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RET	PONATINIB
MEN1	LOPERAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
RET	135	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	RET
SORAFENIB	4	MEN1, RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	RET
VANDETANIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	RET
BRIGATINIB	4	RET
UPADACITINIB	4	RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RET	1,586	Binding:1573, Functional:10, ADMET:3
MEN1	93	Binding:86, Functional:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RET	1,586

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

26 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	RET
BRIGATINIB	4	RET
UPADACITINIB	4	RET

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RET, MEN1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 101.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	42
PHASE2	22
PHASE1	15
PHASE1/PHASE2	12
PHASE3	5
PHASE4	3
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01896479	PHASE4	ACTIVE_NOT_RECRUITING	A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer
NCT05830500	PHASE4	RECRUITING	Study of Anlotinib in Patients With Advanced Medullary Thyroid Carcinoma
NCT01915485	PHASE4	UNKNOWN	Radiolabeled Molecules for Medullary Thyroid Cancer
NCT04211337	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
NCT07383246	PHASE3	RECRUITING	CTR-FAPI-guided Precision Surgery for Newly Diagnosed MTC
NCT01298323	PHASE3	COMPLETED	Study to Determine if Contacting Patients With MTC More Frequently Results in Earlier Detection and Treatment of Signs and Symptoms of AEs and Thus a Decrease in the Percentage of Time Patients Experience AEs During First 12 Months on Vandetanib Treatment
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT02586350	PHASE2/PHASE3	COMPLETED	Study of Anlotinib in Patients With Medullary Thyroid Carcinoma(ALTER01031)
NCT04760288	PHASE3	WITHDRAWN	A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC).
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03157128	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
NCT03899792	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
NCT04280081	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation
NCT04759911	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer
NCT06121271	PHASE2	NOT_YET_RECRUITING	Trial of Lu-177 DOTATATE (Lutathera®) in Unlicensed Indications
NCT06814496	PHASE1/PHASE2	RECRUITING	Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors
NCT00118248	PHASE2	COMPLETED	Tanespimycin in Treating Patients With Inoperable Locoregionally Advanced or Metastatic Thyroid Cancer
NCT00134043	PHASE2	COMPLETED	Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer
NCT00381641	PHASE2	COMPLETED	Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery
NCT00390325	PHASE2	COMPLETED	Sorafenib Tosylate in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer
NCT00514046	PHASE1/PHASE2	COMPLETED	Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer
NCT00519896	PHASE2	COMPLETED	Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer
NCT00582712	PHASE2	TERMINATED	An Initial Study of Lithium in Patients With Medullary Thyroid Cancer
NCT00625846	PHASE2	COMPLETED	Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer
NCT00647140	PHASE2	TERMINATED	Clinical Evaluation of 18F-DOPA Positron Emission Tomography in Medullary Thyroid Cancer
NCT00654238	PHASE2	COMPLETED	Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer
NCT00923247	PHASE1/PHASE2	TERMINATED	A Targeted Phase I/II Trial of ZD6474 (Vandetanib; ZACTIMA) Plus the Proteasome Inhibitor, Bortezomib (Velcade ), in Adults With Solid Tumors With a Focus on Hereditary or Sporadic, Locally Advanced or Metastatic Medullary Thyroid Cancer (MTC)
NCT01625520	PHASE2	COMPLETED	SOM230 Alone or in Combination With RAD001 in Patients With Medullary Thyroid Cancer
NCT01730638	PHASE1/PHASE2	COMPLETED	ImmunoTEP for Patients With Medullary Thyroid Carcinoma.
NCT01736878	PHASE2	WITHDRAWN	Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma
NCT01739634	PHASE1/PHASE2	UNKNOWN	The Efficacy of CASAD in Patients With Diarrhea Related to Medullary Thyroid Cancer
NCT01788982	PHASE2	COMPLETED	Nintedanib(BIBF1120) in Thyroid Cancer
NCT01856920	PHASE2	COMPLETED	QUILT-3.006 for Recurrent Medullary Thyroid Cancer
NCT02709889	PHASE1/PHASE2	TERMINATED	Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
NCT03037385	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
NCT03072160	PHASE2	COMPLETED	Pembrolizumab in Recurrent or Metastatic Medullary Thyroid Cancer
NCT03630120	PHASE2	TERMINATED	Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer
NCT03838692	PHASE2	WITHDRAWN	Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer
NCT04106843	PHASE2	WITHDRAWN	Radioactive Drug (177Lu-DOTATATE) for the Treatment of Locally Advanced, Metastatic, or Unresectable Rare Endocrine Cancers
NCT04161391	PHASE1/PHASE2	TERMINATED	Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	12
VANDETANIB	4	7
SELPERCATINIB	4	6
SUNITINIB	4	6
PRALSETINIB	4	3
EDOTREOTIDE GALLIUM GA-68	4	1
ESOMEPRAZOLE	4	1
FERUMOXYTOL	4	1
FLUORODOPA F 18	4	1
LITHIUM CARBONATE	4	1
LUTETIUM OXODOTREOTIDE LU-177	4	1
NINTEDANIB	4	1
OCTREOTIDE ACETATE	4	1
PAZOPANIB HYDROCHLORIDE	4	1
PONATINIB	4	1
RANITIDINE	4	1
SORAFENIB	4	1
TARLATAMAB	4	1
VORINOSTAT	4	1
CATEQUENTINIB	3	2
VATALANIB	3	2
VELIPARIB	3	2
ROVALPITUZUMAB TESIRINE	3	1
TANESPIMYCIN	3	1
THYROID	3	1
CIXUTUMUMAB	2	1
EDODEKIN ALFA	2	1
ENBEZOTINIB	2	1
FAPI-46 GA-68	2	1
PP-F11N LUTETIUM LU-177	1	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 18 predictive associations from 23 curated evidence items; also 3 predisposing, 2 oncogenic, 2 prognostic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
RET Mutation	Selpercatinib	Sensitivity/Response	CIViC A	EID12157 +2
RET M918T	Selpercatinib	Sensitivity/Response	CIViC A	EID12598
RET E632_L633del	Selpercatinib	Sensitivity/Response	CIViC B	EID11875 +2
RET M918T	Sorafenib	Sensitivity/Response	CIViC B	EID1365
RET M918T	Cabozantinib	Sensitivity/Response	CIViC B	EID7710
RET Mutation	Cabozantinib	Sensitivity/Response	CIViC B	EID8984
RET V804M	Selpercatinib	Sensitivity/Response	CIViC C	EID6951 +1
RET D378_G685>E	Selpercatinib	Sensitivity/Response	CIViC C	EID11658
RET M918T AND RET V804M	Selpercatinib	Sensitivity/Response	CIViC C	EID6950
RET G810S	Pralsetinib + Selpercatinib	Resistance	CIViC C	EID8919
RET M918T AND RET G810S	Selpercatinib	Resistance	CIViC C	EID8196
RET Y806C	Pralsetinib + Selpercatinib	Resistance	CIViC C	EID8920
RET Y806N	Pralsetinib + Selpercatinib	Resistance	CIViC C	EID8921
RET M918T	JAK2 Inhibitor AZD1480	Sensitivity/Response	CIViC D	EID77
RET C634W	Axitinib	Resistance	CIViC D	EID3694
RET C634W	Motesanib	Resistance	CIViC D	EID75
RET M918T	Axitinib	Resistance	CIViC D	EID3696
RET M918T	Motesanib	Resistance	CIViC D	EID76