Liposarcoma

disease
On this page

Also known as lip sarcomaliposarcoma, malignantsarcoma of lip

Summary

Liposarcoma (MONDO:0005060) is a disease (an umbrella term covering 19 Mondo subtypes) with 1 cohort gene and 63 clinical trials. Molecularly, CDK4 Amplification confers sensitivity to Palbociclib in Liposarcoma (CIViC Level B); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include pazopanib, trabectedin, and dexrazoxane.

At a glance

  • Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
  • Umbrella term: 19 Mondo subtypes
  • Cohort genes: 1
  • Phenotypes (HPO): 9
  • Clinical trials: 63
  • Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Annual incidence1-9 / 100 0001EuropeValidated
Annual incidence1-9 / 1 000 0000.59United StatesValidated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO IDTermFrequency
HP:0001482Subcutaneous noduleVery frequent (80-99%)
HP:0100242SarcomaVery frequent (80-99%)
HP:0000077Abnormality of the kidneyOccasional (5-29%)
HP:0001824Weight lossOccasional (5-29%)
HP:0002017Nausea and vomitingOccasional (5-29%)
HP:0002027Abdominal painOccasional (5-29%)
HP:0002619Varicose veinsOccasional (5-29%)
HP:0003401ParesthesiaOccasional (5-29%)
HP:0012378FatigueOccasional (5-29%)

Identifiers

Disease identifiers

FieldValue
Canonical nameliposarcoma
Mondo IDMONDO:0005060
EFOEFO:0000569
MeSHD008080
Orphanet69078
DOIDDOID:3382
NCITC3194
SNOMED CT254829001
UMLSC0023827
MedGen44177
GARD0006913
MedDRA10024627
NORD1925
Is cancer (heuristic)no

Also known as: lip sarcoma · liposarcoma · liposarcoma, malignant · sarcoma of lip

Data availability: 25 cell lines · 6 intOGen driver records.

Disease family

An umbrella term covering 19 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumorneoplastic disease or syndromeneoplasmcancer › lipomatous cancer › liposarcoma

Subtypes (19): liposarcoma of bone, adult liposarcoma, esophagus liposarcoma, pediatric liposarcoma, larynx liposarcoma, liposarcoma of the ovary, fibroblastic liposarcoma, kidney liposarcoma, gastric liposarcoma, breast liposarcoma, mixed liposarcoma, vulvar liposarcoma, cutaneous liposarcoma, mediastinum liposarcoma, intracranial liposarcoma, well-differentiated liposarcoma, myxoid/round cell liposarcoma, pleomorphic liposarcoma, dedifferentiated liposarcoma

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CDK4Orphanet:618Familial melanoma
CDK4Orphanet:99970Dedifferentiated liposarcoma
CDK4Orphanet:99971Well-differentiated liposarcoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CDK4HGNC:1773ENSG00000135446P11802Cyclin-dependent kinase 4civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CDK4Cyclin-dependent kinase 4Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.

Protein-family classification

Druggable: 1 · 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.

FamilyGenesFoldFDR
Kinase127.7×0.036

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CDK4Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
embryo1
ganglionic eminence1
ventricular zone1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CDK4138ubiquitousmarkerembryo, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CDK48,412

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CDK4P1180215

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK415710.0×0.002CDK4
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK415710.0×0.002CDK4
Diseases of Cellular Senescence13806.7×0.002CDK4
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects13806.7×0.002CDK4
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK613806.7×0.002CDK4
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects13806.7×0.002CDK4
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK613806.7×0.002CDK4
Diseases of cellular response to stress13806.7×0.002CDK4
Drug-mediated inhibition of CDK4/CDK6 activity12284.0×0.002CDK4
PTK6 Regulates Cell Cycle11903.3×0.003CDK4
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects1878.5×0.005CDK4
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)1634.4×0.007CDK4
Signaling by PTK61543.8×0.007CDK4
Signaling by Non-Receptor Tyrosine Kinases1543.8×0.007CDK4
Aberrant regulation of mitotic cell cycle due to RB1 defects1407.9×0.007CDK4
G1 Phase1393.8×0.007CDK4
Diseases of mitotic cell cycle1393.8×0.007CDK4
Oncogene Induced Senescence1335.9×0.008CDK4
Meiosis1285.5×0.008CDK4
Cyclin E associated events during G1/S transition1285.5×0.008CDK4
Cyclin A:Cdk2-associated events at S phase entry1265.6×0.008CDK4
Ubiquitin-dependent degradation of Cyclin D1265.6×0.008CDK4
Transcriptional regulation by RUNX21253.8×0.008CDK4
G1/S Transition1233.1×0.008CDK4
Cyclin D associated events in G11233.1×0.008CDK4
SPOP-mediated proteasomal degradation of PD-L1(CD274)1228.4×0.008CDK4
SCF(Skp2)-mediated degradation of p27/p211207.6×0.009CDK4
Reproduction1190.3×0.009CDK4
Mitotic G1 phase and G1/S transition1184.2×0.009CDK4
S Phase1181.3×0.009CDK4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of transcription initiation by RNA polymerase II15617.3×0.002CDK4
cellular response to ionomycin12808.7×0.002CDK4
regulation of type B pancreatic cell proliferation12106.5×0.002CDK4
regulation of G2/M transition of mitotic cell cycle11296.3×0.002CDK4
cellular response to phorbol 13-acetate 12-myristate11296.3×0.002CDK4
cellular response to interleukin-41648.1×0.004CDK4
positive regulation of G2/M transition of mitotic cell cycle1601.9×0.004CDK4
positive regulation of fibroblast proliferation1295.6×0.007CDK4
G1/S transition of mitotic cell cycle1200.6×0.009CDK4
cellular response to lipopolysaccharide198.0×0.016CDK4
regulation of gene expression183.4×0.017CDK4
regulation of cell cycle174.6×0.018CDK4
response to xenobiotic stimulus169.1×0.018CDK4
cell division146.2×0.025CDK4
positive regulation of cell population proliferation133.6×0.032CDK4
signal transduction116.1×0.062CDK4

Therapeutics

Drugs indicated for this disease

1 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
TrabectedinApproved (phase 4)
IfosfamidePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bevacizumab, Doxorubicin, Palbociclib, Pazopanib, Regorafenib, Ribociclib, Ridaforolimus, Selinexor, Sitravatinib.

Drug target analysis

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

Druggability breadth: 1 of 1 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.

SymbolExample approved molecule
CDK4PALBOCICLIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CDK4564

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PALBOCICLIB4CDK4
ABEMACICLIB4CDK4
RIBOCICLIB4CDK4
TRILACICLIB4CDK4
FEDRATINIB4CDK4
DABRAFENIB4CDK4
CERITINIB4CDK4
ENCORAFENIB4CDK4
GILTERITINIB4CDK4
NINTEDANIB4CDK4
SUNITINIB4CDK4
DINACICLIB3CDK4
LEROCICLIB3CDK4
ALVOCIDIB3CDK4
QUERCETIN3CDK4
DALPICICLIB3CDK4
DOVITINIB3CDK4
LESTAURTINIB3CDK4
RUBOXISTAURIN3CDK4
INDIRUBIN2CDK4
SELICICLIB2CDK4
REBASTINIB2CDK4
NARAZACICLIB2CDK4
RIVICICLIB2CDK4
RG-5472CDK4
VORUCICLIB2CDK4
ULECACICLIB2CDK4
CROZBACICLIB2CDK4
RONICICLIB2CDK4
EBVACICLIB2CDK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
CDK41,142Binding:1086, Functional:53, ADMET:2, Toxicity:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CDK42.7.11.22cyclin-dependent kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CDK41,142

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
ABEMACICLIB4CDK4
TRILACICLIB4CDK4
FEDRATINIB4CDK4
DABRAFENIB4CDK4
CERITINIB4CDK4
ENCORAFENIB4CDK4
GILTERITINIB4CDK4
NINTEDANIB4CDK4
SUNITINIB4CDK4
DINACICLIB3CDK4
LEROCICLIB3CDK4
ALVOCIDIB3CDK4
QUERCETIN3CDK4
DALPICICLIB3CDK4
DOVITINIB3CDK4
LESTAURTINIB3CDK4
RUBOXISTAURIN3CDK4
INDIRUBIN2CDK4
SELICICLIB2CDK4
REBASTINIB2CDK4
NARAZACICLIB2CDK4
RIVICICLIB2CDK4
RG-5472CDK4
VORUCICLIB2CDK4
ULECACICLIB2CDK4
CROZBACICLIB2CDK4
RONICICLIB2CDK4
EBVACICLIB2CDK4

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CDK4
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

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: 63.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE227
PHASE115
Not specified9
PHASE1/PHASE28
PHASE32
PHASE2/PHASE31
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02180867PHASE2/PHASE3ACTIVE_NOT_RECRUITINGRadiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery
NCT04031677PHASE3RECRUITINGSurgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma
NCT03773510PHASE3WITHDRAWNStudy on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin
NCT02275286PHASE1/PHASE2RECRUITINGTrabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients
NCT02923778PHASE2ACTIVE_NOT_RECRUITINGTalimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery
NCT04557449PHASE2ACTIVE_NOT_RECRUITINGStudy to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
NCT04785196PHASE1/PHASE2RECRUITINGAPG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Advanced Solid Tumors
NCT05836571PHASE2ACTIVE_NOT_RECRUITINGTesting Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma
NCT06239272PHASE1/PHASE2RECRUITINGNRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06277154PHASE2RECRUITINGMASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma
NCT06541262PHASE1/PHASE2RECRUITINGSilmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
NCT06843967PHASE1/PHASE2RECRUITINGA Study of Mirdametinib in Combination With Palbociclib in People With Liposarcoma
NCT07169344PHASE2RECRUITINGHypofractionated, 3-week, Preoperative Proton or X-ray Radiotherapy for Patients With Localized Soft Tissue Sarcoma
NCT07173972PHASE2RECRUITINGDose-escalated, Hypofractionated, Definitive Proton Radiotherapy for Patients With Inoperable Soft Tissue Sarcoma.
NCT00060944PHASE2COMPLETEDA Study to Assess Treatment With 2 Different Dosing Schedules of Trabectidin Administered to Patients With Advanced Cancer
NCT00093080PHASE2COMPLETEDStudy of AP23573/MK-8669 (Ridaforolimus), A Mammalian Target of Rapamycin (mTOR) Inhibitor, in Participants With Advanced Sarcoma (MK-8669-018 AM1)(COMPLETED)
NCT00356031PHASE2COMPLETEDBevacizumab and Radiation Therapy for Sarcomas
NCT00400569PHASE2COMPLETEDPhase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma
NCT01209598PHASE2COMPLETEDPD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma
NCT01506596PHASE2COMPLETEDStudy of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma
NCT01653028PHASE2COMPLETEDAlisertib in Treating Patients With Advanced or Metastatic Sarcoma
NCT02048371PHASE2COMPLETEDSARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes
NCT02247544PHASE2COMPLETEDEfficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
NCT02249949PHASE2COMPLETEDEfatutazone Dihydrochloride in Treating Patients With Previously Treated Myxoid Liposarcoma That Cannot Be Removed by Surgery
NCT02357810PHASE2COMPLETEDPazopanib Hydrochloride and Topotecan Hydrochloride in Treating Patients With Metastatic Soft Tissue and Bone Sarcomas
NCT02500797PHASE2COMPLETEDNivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery
NCT02571829PHASE2UNKNOWNA Phase II Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma
NCT02584309PHASE2COMPLETEDDoxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
NCT02609984PHASE2TERMINATEDStudy to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
NCT02978859PHASE2COMPLETEDSitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas
NCT03074318PHASE1/PHASE2TERMINATEDAvelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery
NCT03526679PHASE1/PHASE2COMPLETEDLenvatinib and Eribulin in Advanced Soft Tissue Sarcoma
NCT03651375PHASE2UNKNOWNHypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall
NCT03899805PHASE2COMPLETEDA Phase II Study of Eribulin and Pembrolizumab in Soft Tissue Sarcomas
NCT04906876PHASE2WITHDRAWNA Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
NCT05094804PHASE1/PHASE2UNKNOWNA Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
NCT05116683PHASE2TERMINATEDATX-101 in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma
NCT05116800PHASE2WITHDRAWNPhase 2 Study of 9-ING-41 With Chemotherapy in Sarcoma
NCT03361436PHASE1ACTIVE_NOT_RECRUITINGEribulin and Radiation Therapy in Treating Patients With Retroperitoneal Liposarcoma That Can Be Removed by Surgery
NCT04377932PHASE1ACTIVE_NOT_RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PAZOPANIB46
TRABECTEDIN46
DEXRAZOXANE43
ERIBULIN43
IFOSFAMIDE43
AVELUMAB41
CABOZANTINIB41
CEMIPLIMAB41
DEOXYCHOLIC ACID41
PALBOCICLIB41
REGORAFENIB41
RIBOCICLIB41
SELINEXOR41
SODIUM THIOSULFATE41
SUNITINIB MALATE41
TALIMOGENE LAHERPAREPVEC41
TOPOTECAN HYDROCHLORIDE41
ALISERTIB31
IXAZOMIB31
RIDAFOROLIMUS31
SITRAVATINIB31
ZANZALINTINIB31
ELRAGLUSIB22
ATIRMOCICLIB21
EFATUTAZONE21
MIRDAMETINIB21
SILMITASERTIB21
SIREMADLIN21
BTX-A5111
EFROFILCON A11

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 3 curated evidence items; also 3 diagnostic.

Molecular subtypeTherapyEffectLevelCIViC
CDK4 AmplificationPalbociclibSensitivity/ResponseCIViC BEID1366 +1
MDM2 AmplificationHDM2 Inhibitor MK-8242Sensitivity/ResponseCIViC CEID5518