Adult liposarcoma

Summary

Adult liposarcoma (MONDO:0003585) is a disease with 1 cohort gene and 71 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 ifosfamide.

At a glance

• Cohort genes: 1
• Clinical trials: 71
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	adult liposarcoma
Mondo ID	MONDO:0003585
DOID	DOID:5693
NCIT	C7811
UMLS	C0278608
MedGen	75842
GARD	0023569
Is cancer (heuristic)	no

Also known as: adult liposarcoma · liposarcoma · liposarcoma of adults

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

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › lipomatous cancer › liposarcoma › adult liposarcoma

Related subtypes (18): liposarcoma of bone, 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)

Gene	Orphanet ID	Rare disease
CDK4	Orphanet:618	Familial melanoma
CDK4	Orphanet:99970	Dedifferentiated liposarcoma
CDK4	Orphanet:99971	Well-differentiated liposarcoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDK4	HGNC:1773	ENSG00000135446	P11802	Cyclin-dependent kinase 4	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDK4	Cyclin-dependent kinase 4	Ser/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.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDK4	Kinase	yes	2.7.11.22	Prot_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)

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

Top tissues across cohort

Tissue	Cohort genes
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDK4	138	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDK4	8,412

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDK4	P11802	15

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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	5710.0×	0.002	CDK4
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	5710.0×	0.002	CDK4
Diseases of Cellular Senescence	1	3806.7×	0.002	CDK4
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	3806.7×	0.002	CDK4
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	3806.7×	0.002	CDK4
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	3806.7×	0.002	CDK4
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	3806.7×	0.002	CDK4
Diseases of cellular response to stress	1	3806.7×	0.002	CDK4
Drug-mediated inhibition of CDK4/CDK6 activity	1	2284.0×	0.002	CDK4
PTK6 Regulates Cell Cycle	1	1903.3×	0.003	CDK4
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1	878.5×	0.005	CDK4
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	634.4×	0.007	CDK4
Signaling by PTK6	1	543.8×	0.007	CDK4
Signaling by Non-Receptor Tyrosine Kinases	1	543.8×	0.007	CDK4
Aberrant regulation of mitotic cell cycle due to RB1 defects	1	407.9×	0.007	CDK4
G1 Phase	1	393.8×	0.007	CDK4
Diseases of mitotic cell cycle	1	393.8×	0.007	CDK4
Oncogene Induced Senescence	1	335.9×	0.008	CDK4
Meiosis	1	285.5×	0.008	CDK4
Cyclin E associated events during G1/S transition	1	285.5×	0.008	CDK4
Cyclin A:Cdk2-associated events at S phase entry	1	265.6×	0.008	CDK4
Ubiquitin-dependent degradation of Cyclin D	1	265.6×	0.008	CDK4
Transcriptional regulation by RUNX2	1	253.8×	0.008	CDK4
G1/S Transition	1	233.1×	0.008	CDK4
Cyclin D associated events in G1	1	233.1×	0.008	CDK4
SPOP-mediated proteasomal degradation of PD-L1(CD274)	1	228.4×	0.008	CDK4
SCF(Skp2)-mediated degradation of p27/p21	1	207.6×	0.009	CDK4
Reproduction	1	190.3×	0.009	CDK4
Mitotic G1 phase and G1/S transition	1	184.2×	0.009	CDK4
S Phase	1	181.3×	0.009	CDK4

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 term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of transcription initiation by RNA polymerase II	1	5617.3×	0.002	CDK4
cellular response to ionomycin	1	2808.7×	0.002	CDK4
regulation of type B pancreatic cell proliferation	1	2106.5×	0.002	CDK4
regulation of G2/M transition of mitotic cell cycle	1	1296.3×	0.002	CDK4
cellular response to phorbol 13-acetate 12-myristate	1	1296.3×	0.002	CDK4
cellular response to interleukin-4	1	648.1×	0.004	CDK4
positive regulation of G2/M transition of mitotic cell cycle	1	601.9×	0.004	CDK4
positive regulation of fibroblast proliferation	1	295.6×	0.007	CDK4
G1/S transition of mitotic cell cycle	1	200.6×	0.009	CDK4
cellular response to lipopolysaccharide	1	98.0×	0.016	CDK4
regulation of gene expression	1	83.4×	0.017	CDK4
regulation of cell cycle	1	74.6×	0.018	CDK4
response to xenobiotic stimulus	1	69.1×	0.018	CDK4
cell division	1	46.2×	0.025	CDK4
positive regulation of cell population proliferation	1	33.6×	0.032	CDK4
signal transduction	1	16.1×	0.062	CDK4

Therapeutics

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.

Symbol	Example approved molecule
CDK4	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK4	56	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	CDK4
ABEMACICLIB	4	CDK4
RIBOCICLIB	4	CDK4
TRILACICLIB	4	CDK4
FEDRATINIB	4	CDK4
DABRAFENIB	4	CDK4
CERITINIB	4	CDK4
ENCORAFENIB	4	CDK4
GILTERITINIB	4	CDK4
NINTEDANIB	4	CDK4
SUNITINIB	4	CDK4
DINACICLIB	3	CDK4
LEROCICLIB	3	CDK4
ALVOCIDIB	3	CDK4
QUERCETIN	3	CDK4
DALPICICLIB	3	CDK4
DOVITINIB	3	CDK4
LESTAURTINIB	3	CDK4
RUBOXISTAURIN	3	CDK4
INDIRUBIN	2	CDK4
SELICICLIB	2	CDK4
REBASTINIB	2	CDK4
NARAZACICLIB	2	CDK4
RIVICICLIB	2	CDK4
RG-547	2	CDK4
VORUCICLIB	2	CDK4
ULECACICLIB	2	CDK4
CROZBACICLIB	2	CDK4
RONICICLIB	2	CDK4
EBVACICLIB	2	CDK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CDK4	1,142	Binding:1086, Functional:53, ADMET:2, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDK4	2.7.11.22	cyclin-dependent kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CDK4	1,142

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.

Compound	Max phase	Cohort target (bioactivity)
ABEMACICLIB	4	CDK4
TRILACICLIB	4	CDK4
FEDRATINIB	4	CDK4
DABRAFENIB	4	CDK4
CERITINIB	4	CDK4
ENCORAFENIB	4	CDK4
GILTERITINIB	4	CDK4
NINTEDANIB	4	CDK4
SUNITINIB	4	CDK4
DINACICLIB	3	CDK4
LEROCICLIB	3	CDK4
ALVOCIDIB	3	CDK4
QUERCETIN	3	CDK4
DALPICICLIB	3	CDK4
DOVITINIB	3	CDK4
LESTAURTINIB	3	CDK4
RUBOXISTAURIN	3	CDK4
INDIRUBIN	2	CDK4
SELICICLIB	2	CDK4
REBASTINIB	2	CDK4
NARAZACICLIB	2	CDK4
RIVICICLIB	2	CDK4
RG-547	2	CDK4
VORUCICLIB	2	CDK4
ULECACICLIB	2	CDK4
CROZBACICLIB	2	CDK4
RONICICLIB	2	CDK4
EBVACICLIB	2	CDK4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CDK4
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: 71.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	30
PHASE1	17
PHASE1/PHASE2	10
Not specified	9
PHASE3	3
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02180867	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Radiation 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
NCT04031677	PHASE3	RECRUITING	Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma
NCT00346164	PHASE3	COMPLETED	Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
NCT03773510	PHASE3	WITHDRAWN	Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin
NCT02275286	PHASE1/PHASE2	RECRUITING	Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients
NCT02923778	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery
NCT04557449	PHASE2	ACTIVE_NOT_RECRUITING	Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
NCT04785196	PHASE1/PHASE2	RECRUITING	APG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Advanced Solid Tumors
NCT05836571	PHASE2	ACTIVE_NOT_RECRUITING	Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06277154	PHASE2	RECRUITING	MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma
NCT06541262	PHASE1/PHASE2	RECRUITING	Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
NCT06843967	PHASE1/PHASE2	RECRUITING	A Study of Mirdametinib in Combination With Palbociclib in People With Liposarcoma
NCT07169344	PHASE2	RECRUITING	Hypofractionated, 3-week, Preoperative Proton or X-ray Radiotherapy for Patients With Localized Soft Tissue Sarcoma
NCT07173972	PHASE2	RECRUITING	Dose-escalated, Hypofractionated, Definitive Proton Radiotherapy for Patients With Inoperable Soft Tissue Sarcoma.
NCT00060944	PHASE2	COMPLETED	A Study to Assess Treatment With 2 Different Dosing Schedules of Trabectidin Administered to Patients With Advanced Cancer
NCT00093080	PHASE2	COMPLETED	Study of AP23573/MK-8669 (Ridaforolimus), A Mammalian Target of Rapamycin (mTOR) Inhibitor, in Participants With Advanced Sarcoma (MK-8669-018 AM1)(COMPLETED)
NCT00112463	PHASE2	COMPLETED	Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma
NCT00233948	PHASE1/PHASE2	TERMINATED	Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma
NCT00356031	PHASE2	COMPLETED	Bevacizumab and Radiation Therapy for Sarcomas
NCT00400569	PHASE2	COMPLETED	Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma
NCT00659360	PHASE2	COMPLETED	AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma
NCT01154452	PHASE1/PHASE2	COMPLETED	Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma
NCT01209598	PHASE2	COMPLETED	PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma
NCT01506596	PHASE2	COMPLETED	Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma
NCT01532687	PHASE2	COMPLETED	Gemcitabine With or Without Pazopanib in Treating Patients With Refractory Soft Tissue Sarcoma
NCT01653028	PHASE2	COMPLETED	Alisertib in Treating Patients With Advanced or Metastatic Sarcoma
NCT02048371	PHASE2	COMPLETED	SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes
NCT02247544	PHASE2	COMPLETED	Efficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
NCT02249949	PHASE2	COMPLETED	Efatutazone Dihydrochloride in Treating Patients With Previously Treated Myxoid Liposarcoma That Cannot Be Removed by Surgery
NCT02357810	PHASE2	COMPLETED	Pazopanib Hydrochloride and Topotecan Hydrochloride in Treating Patients With Metastatic Soft Tissue and Bone Sarcomas
NCT02500797	PHASE2	COMPLETED	Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery
NCT02571829	PHASE2	UNKNOWN	A Phase II Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma
NCT02584309	PHASE2	COMPLETED	Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
NCT02609984	PHASE2	TERMINATED	Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
NCT02978859	PHASE2	COMPLETED	Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas
NCT03074318	PHASE1/PHASE2	TERMINATED	Avelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery
NCT03526679	PHASE1/PHASE2	COMPLETED	Lenvatinib and Eribulin in Advanced Soft Tissue Sarcoma
NCT03651375	PHASE2	UNKNOWN	Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall
NCT03899805	PHASE2	COMPLETED	A Phase II Study of Eribulin and Pembrolizumab in Soft Tissue Sarcomas

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PAZOPANIB	4	9
TRABECTEDIN	4	6
IFOSFAMIDE	4	4
DEXRAZOXANE	4	3
ERIBULIN	4	3
AVELUMAB	4	1
CEMIPLIMAB	4	1
DEOXYCHOLIC ACID	4	1
NELFINAVIR MESYLATE	4	1
PALBOCICLIB	4	1
REGORAFENIB	4	1
RIBOCICLIB	4	1
ROMIDEPSIN	4	1
SELINEXOR	4	1
SODIUM THIOSULFATE	4	1
SUNITINIB MALATE	4	1
TALIMOGENE LAHERPAREPVEC	4	1
TOPOTECAN HYDROCHLORIDE	4	1
TORIPALIMAB	4	1
VISMODEGIB	4	1
ALISERTIB	3	1
IXAZOMIB	3	1
RIDAFOROLIMUS	3	1
SARACATINIB	3	1
SITRAVATINIB	3	1
ZANZALINTINIB	3	1
ELRAGLUSIB	2	2
ATIRMOCICLIB	2	1
CIXUTUMUMAB	2	1
EFATUTAZONE	2	1

Precision-medicine subtype map (CIViC)

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

Molecular subtype	Therapy	Effect	Level	CIViC
CDK4 Amplification	Palbociclib	Sensitivity/Response	CIViC B	EID1366 +1
MDM2 Amplification	HDM2 Inhibitor MK-8242	Sensitivity/Response	CIViC C	EID5518