Familial medullary thyroid carcinoma

Summary

Familial medullary thyroid carcinoma (MONDO:0007958) is a cancer caused by RET (GenCC Definitive), with 4 cohort genes (3 CIViC-evidence somatic drivers; 384 ClinVar predisposition records) and 20 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 vandetanib and catequentinib.

At a glance

• Classification: Cancer
• Causal gene: RET (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 384
• Clinical trials: 20
• Precision-medicine evidence (CIViC): 18 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial medullary thyroid carcinoma
Mondo ID	MONDO:0007958
MeSH	C536911
OMIM	155240
Orphanet	99361
DOID	DOID:0050547
NCIT	C46099
UMLS	C1833921
MedGen	322311
GARD	0016901
Is cancer (heuristic)	yes

Also known as: familial medullary thyroid carcinoma · familial MTC · hereditary medullary thyroid gland carcinoma · hereditary thyroid medullary carcinoma · medullary thyroid carcinoma · MTC · thyroid carcinoma, familial medullary

Data availability: 384 ClinVar variants · 4 GenCC gene-disease records · 16 cell lines.

Disease family

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 › 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

384 retrieved; paginated sample, class counts are floors:

155 uncertain significance, 138 conflicting classifications of pathogenicity, 32 likely benign, 31 benign/likely benign, 18 pathogenic, 7 pathogenic/likely pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
978717	NM_002529.4(NTRK1):c.1768G>A (p.Glu590Lys)	NTRK1	Pathogenic	criteria provided, single submitter
13905	NM_020975.6(RET):c.1852T>G (p.Cys618Gly)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13908	NM_020975.6(RET):c.1900T>G (p.Cys634Gly)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13909	NM_020975.6(RET):c.1901G>A (p.Cys634Tyr)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13911	NM_020975.6(RET):c.1901G>T (p.Cys634Phe)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13914	NM_020975.6(RET):c.1853G>C (p.Cys618Ser)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13916	NM_020975.6(RET):c.1859G>A (p.Cys620Tyr)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13919	NM_020975.6(RET):c.2753T>C (p.Met918Thr)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13928	NM_020975.6(RET):c.1859G>T (p.Cys620Phe)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13929	NM_020975.6(RET):c.1852T>C (p.Cys618Arg)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13931	NM_020975.6(RET):c.2304G>C (p.Glu768Asp)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13933	NM_020975.6(RET):c.1826G>A (p.Cys609Tyr)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13935	NM_020975.6(RET):c.2370G>C (p.Leu790Phe)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13941	NM_020975.6(RET):c.1586_1594dup (p.Cys531_Gly532insGluGluCys)	RET	Pathogenic	no assertion criteria provided
13943	NM_020975.6(RET):c.1859G>C (p.Cys620Ser)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13944	NM_020975.6(RET):c.1825T>C (p.Cys609Arg)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13946	NM_020975.6(RET):c.2410G>T (p.Val804Leu)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13950	NM_020975.6(RET):c.1597G>T (p.Gly533Cys)	RET	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
230926	NM_020975.6(RET):c.1998G>C (p.Lys666Asn)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
24929	NM_020975.6(RET):c.1947G>A (p.Ser649=)	RET	Pathogenic/Likely 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
24932	NM_020975.6(RET):c.1998G>T (p.Lys666Asn)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37102	NM_020975.6(RET):c.2410G>A (p.Val804Met)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
38612	NM_020975.6(RET):c.2370G>T (p.Leu790Phe)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13922	NM_020975.6(RET):c.2914A>G (p.Arg972Gly)	RET	Likely pathogenic	criteria provided, single submitter
1777553	NM_020975.6(RET):c.1664T>G (p.Phe555Cys)	RET	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3595005	NM_020975.6(RET):c.2672C>T (p.Ser891Leu)	RET	Likely pathogenic	criteria provided, single submitter
229201	NM_020975.6(RET):c.-2C>A	LOC106736614	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
477374	NM_020975.6(RET):c.-37G>C	LOC106736614	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 27 · Orphanet: 15 · 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
NTRK1	Act	BRCA	CIViC #3983
ESR2			CIViC #1753

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RET	Definitive	Autosomal dominant	familial medullary thyroid carcinoma	16
ESR2	Supportive	Autosomal dominant	familial medullary thyroid carcinoma	6
NTRK1	Supportive	Autosomal dominant	familial medullary thyroid carcinoma	5

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
NTRK1	Orphanet:146	Differentiated thyroid carcinoma
NTRK1	Orphanet:642	Hereditary sensory and autonomic neuropathy type 4
NTRK1	Orphanet:64752	Hereditary sensory and autonomic neuropathy type 5
NTRK1	Orphanet:99361	Isolated familial medullary thyroid carcinoma
ESR2	Orphanet:99361	Isolated familial medullary thyroid carcinoma

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	gencc,clinvar,civic_evidence
NTRK1	HGNC:8031	ENSG00000198400	P04629	High affinity nerve growth factor receptor	gencc,clinvar
ESR2	HGNC:3468	ENSG00000140009	Q92731	Estrogen receptor beta	gencc
INSRR	HGNC:6093	ENSG00000027644	P14616	Insulin receptor-related protein	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,…
NTRK1	High affinity nerve growth factor receptor	Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons.
ESR2	Estrogen receptor beta	Nuclear hormone receptor.
INSRR	Insulin receptor-related protein	Receptor with tyrosine-protein kinase activity.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	3	20.8×	4e-04
Nuclear receptor	1	96.5×	0.010

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
NTRK1	Kinase	yes	2.7.10.1	Cys-rich_flank_reg_C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ESR2	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
INSRR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	2
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
apex of heart	1
male germ line stem cell (sensu Vertebrata) in testis	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
adult mammalian kidney	1
myocardium	1
skeletal muscle tissue of rectus abdominis	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
NTRK1	160	broad	marker	dorsal root ganglion, apex of heart, male germ line stem cell (sensu Vertebrata) in testis
ESR2	170	broad	yes	right adrenal gland, right adrenal gland cortex, left adrenal gland
INSRR	94	tissue_specific	marker	myocardium, skeletal muscle tissue of rectus abdominis, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NTRK1	9,181
ESR2	5,924
RET	4,203
INSRR	1,866

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NTRK1	P04629	65
ESR2	Q92731	39
RET	P07949	34
INSRR	P14616	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TRKA activation by NGF	1	1903.3×	0.006	NTRK1
PLC-gamma1 signalling	1	1268.9×	0.006	NTRK1
Signalling to STAT3	1	1268.9×	0.006	NTRK1
NGF-independant TRKA activation	1	761.3×	0.006	NTRK1
Signalling to p38 via RIT and RIN	1	761.3×	0.006	NTRK1
ARMS-mediated activation	1	543.8×	0.006	NTRK1
PI3K/AKT activation	1	423.0×	0.007	NTRK1
Frs2-mediated activation	1	317.2×	0.008	NTRK1
Retrograde neurotrophin signalling	1	271.9×	0.009	NTRK1
Signalling to RAS	1	223.9×	0.009	NTRK1
Formation of the nephric duct	1	211.5×	0.009	RET
NPAS4 regulates expression of target genes	1	165.5×	0.010	RET
Formation of the ureteric bud	1	165.5×	0.010	RET
RET signaling	1	86.5×	0.017	RET
Nuclear Receptor transcription pathway	1	66.8×	0.021	ESR2
Extra-nuclear estrogen signaling	1	56.8×	0.023	ESR2
ESR-mediated signaling	1	42.8×	0.027	ESR2
Constitutive Signaling by Aberrant PI3K in Cancer	1	42.3×	0.027	ESR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	32.3×	0.034	ESR2
PIP3 activates AKT signaling	1	22.3×	0.046	ESR2
RAF/MAP kinase cascade	1	20.4×	0.048	RET

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell surface receptor protein tyrosine kinase signaling pathway	3	130.3×	6e-05	RET, NTRK1, INSRR
embryonic epithelial tube formation	1	2106.5×	0.005	RET
posterior midgut development	1	2106.5×	0.005	RET
programmed cell death involved in cell development	1	2106.5×	0.005	NTRK1
cellular response to alkaline pH	1	2106.5×	0.005	INSRR
olfactory nerve development	1	1404.3×	0.005	NTRK1
behavioral response to formalin induced pain	1	1404.3×	0.005	NTRK1
positive regulation of metanephric glomerulus development	1	1404.3×	0.005	RET
ureter maturation	1	1053.2×	0.005	RET
response to hydrostatic pressure	1	1053.2×	0.005	NTRK1
Peyer’s patch morphogenesis	1	1053.2×	0.005	RET
GDF15-GFRAL signaling pathway	1	1053.2×	0.005	RET
protein autophosphorylation	2	72.6×	0.005	NTRK1, INSRR
positive regulation of neuron projection development	2	68.5×	0.005	RET, NTRK1
axon guidance	2	45.3×	0.005	RET, NTRK1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	39.2×	0.005	RET, NTRK1
mechanoreceptor differentiation	1	842.6×	0.006	NTRK1
cellular response to nicotine	1	526.6×	0.009	NTRK1
peptidyl-tyrosine autophosphorylation	1	468.1×	0.009	NTRK1
lymphocyte migration into lymphoid organs	1	468.1×	0.009	RET
axonogenesis involved in innervation	1	421.3×	0.010	NTRK1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	383.0×	0.010	RET
male sex determination	1	351.1×	0.010	INSRR
nerve growth factor signaling pathway	1	324.1×	0.010	NTRK1
positive regulation of cell size	1	324.1×	0.010	RET
glial cell-derived neurotrophic factor receptor signaling pathway	1	300.9×	0.010	RET
positive regulation of programmed cell death	1	280.9×	0.010	NTRK1
detection of mechanical stimulus involved in sensory perception of pain	1	280.9×	0.010	NTRK1
Sertoli cell development	1	280.9×	0.010	NTRK1
membrane protein proteolysis	1	263.3×	0.010	RET

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 4 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
NTRK1	PONATINIB
ESR2	RALOXIFENE HYDROCHLORIDE
INSRR	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RET	135	4
NTRK1	66	4
ESR2	44	4
INSRR	16	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	NTRK1, RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	INSRR, NTRK1, RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	NTRK1, RET
SORAFENIB	4	NTRK1, RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	NTRK1, RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	NTRK1, RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	NTRK1, RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	NTRK1, RET
VANDETANIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	NTRK1, RET
GILTERITINIB	4	RET
BRIGATINIB	4	INSRR, RET
UPADACITINIB	4	RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
RET	1,586	Binding:1573, Functional:10, ADMET:3
NTRK1	1,194	Binding:1182, ADMET:7, Functional:5
ESR2	1,113	Binding:837, Functional:265, ADMET:11
INSRR	251	Binding:250, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RET	2.7.10.1	receptor protein-tyrosine kinase
NTRK1	2.7.10.1	receptor protein-tyrosine kinase
INSRR	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
NTRK1	1,194
ESR2	1,113
INSRR	251

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 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)
PONATINIB	4	NTRK1, RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	INSRR, NTRK1, RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	NTRK1, RET
SORAFENIB	4	NTRK1, RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	NTRK1, RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	NTRK1, RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	NTRK1, RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	NTRK1, RET
NILOTINIB	4	RET
BOSUTINIB	4	NTRK1, RET
GILTERITINIB	4	RET
BRIGATINIB	4	INSRR, RET
UPADACITINIB	4	RET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	RET, NTRK1, ESR2, INSRR
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: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9
PHASE1/PHASE2	3
PHASE2	3
PHASE3	2
PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07383246	PHASE3	RECRUITING	CTR-FAPI-guided Precision Surgery for Newly Diagnosed MTC
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)
NCT06121271	PHASE2	NOT_YET_RECRUITING	Trial of Lu-177 DOTATATE (Lutathera®) in Unlicensed Indications
NCT00514046	PHASE1/PHASE2	COMPLETED	Vandetanib to Treat Children and Adolescents With Medullary 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)
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
NCT04787328	PHASE2	UNKNOWN	A Study of HA121-28 Tablets in Patients With Medullary Thyroid Carcinoma (MTC)
NCT06520319	PHASE1	RECRUITING	Head-to-head Study of 68Ga-MGS5 Versus 68Ga-DOTATATE PET/CT in Patients With Medullary Thyroid Carcinoma
NCT03246659	PHASE1	COMPLETED	Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC
NCT01511393	Not specified	ENROLLING_BY_INVITATION	An Active Surveillance Program for Cases of Medullary Thyroid Carcinoma (MTC)
NCT04970134	Not specified	ACTIVE_NOT_RECRUITING	Spanish Study for Molecular Characterization of Thyroid Carcinoma
NCT06852144	Not specified	ENROLLING_BY_INVITATION	PET-TC in Thyroid Evaluation
NCT07138716	Not specified	RECRUITING	Research on the Application of 68Ga-DOTA-CCK-FS PET/CT in MTC
NCT00880503	Not specified	COMPLETED	Collection of Tissue Samples for Study of Multidrug Resistance
NCT01424878	Not specified	COMPLETED	Study of Molecular Pathways in Medullary Thyroid Carcinoma and Correlation of Molecular Data With Clinical Behavior of the MTC in Individuals Patients
NCT03636945	Not specified	UNKNOWN	Evaluation of 18F-FDOPA PET-CT in the Preoperative Initial Assessment of Medullary Thyroid Carcinoma
NCT05534594	Not specified	COMPLETED	Evaluation of the 18F-PSMA Positron Emission Tomography (PET)/CT in Patients With Medullary Thyroid Cancer
NCT06067594	Not specified	COMPLETED	Calcitonin in Needle Wash Using Electrochemiluminescence Method For Diagnosis Of Medullary Thyroid Carcinoma.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VANDETANIB	4	2
CATEQUENTINIB	3	1

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