Lung sarcomatoid carcinoma

Summary

Lung sarcomatoid carcinoma (MONDO:0006279) is a cancer with 7 cohort genes (7 CIViC-evidence somatic drivers; 10 ClinVar predisposition records) and 2 clinical trials. Molecularly, MET Amplification AND MET Exon 14 Skipping Mutation confers sensitivity to Crizotinib in Lung Sarcomatoid Carcinoma (CIViC Level C); 4 further subtype–drug associations are mapped below. Top therapeutic interventions include ipilimumab and savolitinib.

At a glance

• Classification: Cancer
• Cohort genes: 7
• ClinVar variants: 10
• Clinical trials: 2
• Precision-medicine evidence (CIViC): 5 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lung sarcomatoid carcinoma
Mondo ID	MONDO:0006279
EFO	EFO:1000336
DOID	DOID:0080777
NCIT	C45540
SNOMED CT	707460002
UMLS	C1708781
MedGen	353871
Anatomy (UBERON)	UBERON:0002048
Is cancer (heuristic)	yes

Also known as: lung sarcomatoid carcinoma · sarcomatoid carcinoma of the lung

Data availability: 10 ClinVar variants · 3 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › large cell carcinoma › lung large cell carcinoma › lung sarcomatoid carcinoma

Related subtypes (6): pulmonary large cell neuroendocrine carcinoma, basaloid large cell lung carcinoma, lung occult large cell carcinoma, large cell carcinoma with rhabdoid phenotype, lymphoepithelioma-like lung carcinoma, large cell lung carcinoma, clear cell variant

Subtypes (3): pulmonary blastoma, lung giant cell carcinoma, lung pleomorphic 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

10 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
12583	NM_004985.5(KRAS):c.35G>T (p.Gly12Val)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
2443072	NM_198253.3(TERT):c.-146C>T	LOC110806263	Pathogenic	no assertion criteria provided
634666	NM_000546.6(TP53):c.460_463del (p.Gly154fs)	TP53	Pathogenic	no assertion criteria provided
411977	NM_000551.4(VHL):c.462A>G (p.Pro154=)	LOC107303340	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
659457	NM_000546.6(TP53):c.761T>G (p.Ile254Ser)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2443074	NM_024675.4(PALB2):c.809G>T (p.Ser270Ile)	PALB2	Uncertain significance	no assertion criteria provided
185548	NM_005732.4(RAD50):c.2047G>A (p.Val683Ile)	RAD50	Uncertain significance	criteria provided, multiple submitters, no conflicts
2443073	NM_001378902.1(ROS1):c.6079G>A (p.Asp2027Asn)	ROS1	Uncertain significance	no assertion criteria provided
483809	NM_000179.3(MSH6):c.2055T>C (p.Gly685=)	MSH6	Likely benign	criteria provided, single submitter
414493	NM_006206.6(PDGFRA):c.516C>T (p.Tyr172=)	PDGFRA	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 48 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ROS1	LoF	HCC,HNSC,OVT,PRAD,STAD	CIViC #4941
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
PALB2	LoF	OVT	CIViC #15013
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
MSH6			CIViC #2478
PDGFRA	Act	CSCC,GB,GBM,HGGNOS,LGGNOS,LUSC,PAST	CIViC #38
RAD50	Act	GBM	CIViC #8032

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROS1	Orphanet:251579	Giant cell glioblastoma
ROS1	Orphanet:70567	Cholangiocarcinoma
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma
PALB2	Orphanet:227535	Hereditary breast cancer
PALB2	Orphanet:84	Fanconi anemia
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
RAD50	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD50	Orphanet:240760	Nijmegen breakage syndrome-like disorder

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROS1	HGNC:10261	ENSG00000047936	P08922	Proto-oncogene tyrosine-protein kinase ROS	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	clinvar
RAD50	HGNC:9816	ENSG00000113522	Q92878	DNA repair protein RAD50	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROS1	Proto-oncogene tyrosine-protein kinase ROS	Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
RAD50	DNA repair protein RAD50	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.43

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	2	7.9×	0.121
Scaffold/PPI	1	2.5×	0.744
Enzyme (other)	1	1.7×	0.744
Transcription factor	1	1.2×	0.744
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROS1	Kinase	yes	2.7.10.1	LDLR_classB_rpt, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
RAD50	Other/Unknown	no		Rad50_eukaryotes, Zn_hook_RAD50, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	2
ventricular zone	2
corpus epididymis	1
upper lobe of left lung	1
upper lobe of lung	1
tendon of biceps brachii	1
buccal mucosa cell	1
oocyte	1
secondary oocyte	1
nipple	1
pylorus	1
trigeminal ganglion	1
embryo	1
decidua	1
synovial joint	1
tibia	1
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROS1	79	tissue_specific	marker	upper lobe of left lung, upper lobe of lung, corpus epididymis
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
RAD50	134	ubiquitous	marker	corpus callosum, calcaneal tendon, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
PALB2	5,641
PDGFRA	5,186
MSH6	4,091
RAD50	2,552
ROS1	2,210

Intra-cohort edges

A	B	Sources
KRAS	ROS1	string_interaction
KRAS	TP53	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PDGFRA	P16234	15
MSH6	P52701	8
RAD50	Q92878	6
ROS1	P08922	5
PALB2	Q86YC2	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 153. Enrichment computed across 7 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	292.8×	0.001	KRAS, PDGFRA
Signaling by PDGFRA extracellular domain mutants	2	292.8×	0.001	KRAS, PDGFRA
Impaired BRCA2 binding to PALB2	2	152.3×	0.002	PALB2, RAD50
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	141.0×	0.002	PALB2, RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	141.0×	0.002	PALB2, RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	141.0×	0.002	PALB2, RAD50
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	131.3×	0.002	PALB2, RAD50
Downstream signal transduction	2	126.9×	0.002	KRAS, PDGFRA
Homologous DNA Pairing and Strand Exchange	2	126.9×	0.002	PALB2, RAD50
Resolution of D-loop Structures through Holliday Junction Intermediates	2	100.2×	0.002	PALB2, RAD50
Imatinib-resistant PDGFR mutants	1	1903.3×	0.005	PDGFRA
Sunitinib-resistant PDGFR mutants	1	1903.3×	0.005	PDGFRA
Regorafenib-resistant PDGFR mutants	1	1903.3×	0.005	PDGFRA
Sorafenib-resistant PDGFR mutants	1	1903.3×	0.005	PDGFRA
PDGFR mutants bind TKIs	1	1903.3×	0.005	PDGFRA
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	1903.3×	0.005	TP53
HDR through Homologous Recombination (HRR)	2	63.4×	0.005	PALB2, RAD50
DNA Damage/Telomere Stress Induced Senescence	2	54.4×	0.005	TP53, RAD50
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	48.8×	0.005	TP53, RAD50
Defective Mismatch Repair Associated With MSH6	1	951.7×	0.007	MSH6
Regulation of TP53 Expression	1	951.7×	0.007	TP53
G2/M DNA damage checkpoint	2	40.1×	0.007	TP53, RAD50
Regulation of TP53 Activity through Phosphorylation	2	39.2×	0.007	TP53, RAD50
Defective Mismatch Repair Associated With MSH2	1	634.4×	0.009	MSH6
Signaling by RAS GAP mutants	1	634.4×	0.009	KRAS
Signaling by RAS GTPase mutants	1	634.4×	0.009	KRAS
Mismatch Repair	1	475.8×	0.011	MSH6
Diseases of Mismatch Repair (MMR)	1	475.8×	0.011	MSH6
Transcriptional activation of cell cycle inhibitor p21	1	475.8×	0.011	TP53
Activation of RAS in B cells	1	380.7×	0.013	KRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cellular senescence	2	370.4×	0.003	TP53, KRAS
glial cell proliferation	2	253.4×	0.003	TP53, KRAS
embryonic organ development	2	137.6×	0.006	TP53, PALB2
determination of adult lifespan	2	123.5×	0.006	TP53, MSH6
somitogenesis	2	107.0×	0.006	TP53, PALB2
intrinsic apoptotic signaling pathway	2	102.4×	0.006	TP53, MSH6
meiotic mismatch repair	1	2407.4×	0.007	MSH6
columnar/cuboidal epithelial cell development	1	2407.4×	0.007	ROS1
negative regulation of helicase activity	1	2407.4×	0.007	TP53
response to mineralocorticoid	1	2407.4×	0.007	KRAS
cellular response to actinomycin D	1	2407.4×	0.007	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	2407.4×	0.007	TP53
negative regulation of G1 to G0 transition	1	2407.4×	0.007	TP53
hematopoietic progenitor cell differentiation	2	67.8×	0.007	TP53, PDGFRA
Ras protein signal transduction	2	58.7×	0.007	TP53, KRAS
double-strand break repair	2	58.0×	0.007	TP53, RAD50
regulation of mitotic recombination	1	1203.7×	0.008	RAD50
platelet-derived growth factor receptor-alpha signaling pathway	1	1203.7×	0.008	PDGFRA
positive regulation of mitochondrial membrane permeability	1	1203.7×	0.008	TP53
oligodendrocyte apoptotic process	1	1203.7×	0.008	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	1203.7×	0.008	TP53
negative regulation of pentose-phosphate shunt	1	1203.7×	0.008	TP53
neuron apoptotic process	2	52.9×	0.008	TP53, KRAS
cell surface receptor protein tyrosine kinase signaling pathway	2	49.6×	0.008	ROS1, PDGFRA
double-strand break repair via homologous recombination	2	44.6×	0.008	PALB2, RAD50
obsolete homolactic fermentation	1	802.5×	0.008	TP53
forebrain astrocyte development	1	802.5×	0.008	KRAS
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	802.5×	0.008	PDGFRA
metanephric glomerular capillary formation	1	802.5×	0.008	PDGFRA
signal transduction by p53 class mediator	1	802.5×	0.008	TP53

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 6 · Undrugged: 1

Druggability breadth: 6 of 7 evidence-associated genes (86%) 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
ROS1	LORLATINIB
TP53	NITROFURANTOIN
KRAS	VEMURAFENIB
PDGFRA	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
PDGFRA	77	4
ROS1	41	4
KRAS	11	4
MSH6	1	2
RAD50	1	2
PALB2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LORLATINIB	4	ROS1
BRIGATINIB	4	ROS1
REPOTRECTINIB	4	ROS1
CRIZOTINIB	4	ROS1
FEDRATINIB	4	PDGFRA, ROS1
AXITINIB	4	PDGFRA, ROS1
ALECTINIB	4	ROS1
INFIGRATINIB PHOSPHATE	4	PDGFRA, ROS1
INFIGRATINIB	4	PDGFRA, ROS1
ENTRECTINIB	4	ROS1
CERITINIB	4	PDGFRA, ROS1
GILTERITINIB	4	ROS1
LAROTRECTINIB	4	ROS1
PAZOPANIB	4	PDGFRA, ROS1
NINTEDANIB	4	PDGFRA, ROS1
MITOXANTRONE	4	ROS1, TP53
MIDOSTAURIN	4	PDGFRA, ROS1
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
ROS1	461	Binding:459, Functional:2
MSH6	10	Binding:10
RAD50	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ROS1	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
PDGFRA	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
ROS1	461
TP53	869
KRAS	861
PDGFRA	1,172

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
LORLATINIB	4	ROS1
BRIGATINIB	4	ROS1
REPOTRECTINIB	4	ROS1
CRIZOTINIB	4	ROS1
FEDRATINIB	4	PDGFRA, ROS1
AXITINIB	4	PDGFRA, ROS1
ALECTINIB	4	ROS1
INFIGRATINIB PHOSPHATE	4	PDGFRA, ROS1
INFIGRATINIB	4	PDGFRA, ROS1
ENTRECTINIB	4	ROS1
CERITINIB	4	PDGFRA, ROS1
GILTERITINIB	4	ROS1
LAROTRECTINIB	4	ROS1
PAZOPANIB	4	PDGFRA, ROS1
NINTEDANIB	4	PDGFRA, ROS1
MITOXANTRONE	4	ROS1, TP53
MIDOSTAURIN	4	PDGFRA, ROS1
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	ROS1, TP53, KRAS, PDGFRA
B	Phased (≥1) drug, not yet approved	2	MSH6, RAD50
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PALB2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PALB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT02897479	PHASE2	UNKNOWN	A Phase II Study of HMPL-504 in Lung Sarcomatoid Carcinoma and Other Non-small Cell Lung Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IPILIMUMAB	4	1
SAVOLITINIB	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 5 predictive associations from 5 curated evidence items; also 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
MET Amplification AND MET Exon 14 Skipping Mutation	Crizotinib	Sensitivity/Response	CIViC C	EID11375
MET Exon 14 Skipping Mutation AND CD274 Overexpression	Nivolumab	Sensitivity/Response	CIViC C	EID11414
MET Exon 14 Skipping Mutation AND CD274 Overexpression	Carboplatin/Pemetrexed Regimen + Pembrolizumab	Sensitivity/Response	CIViC C	EID11457
MET Exon 14 Skipping Mutation AND MET Overexpression	Crizotinib	Sensitivity/Response	CIViC C	EID11382
MET Splice Site (c.3028+3A>G)	Crizotinib	Sensitivity/Response	CIViC C	EID11475