Gene

CDK4

cyclin dependent kinase 4

Explore in graph →CI-GENE-00040735HGNC:1773 ENSG00000135446 NCBI 1019 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (9)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–9 of 9 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
CDK4 Amplification2
Palbociclib	Liposarcoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID1366 In a phase 2 clinical trial, NCT01209598, 30 patients with CDK4-amplified and RB-expressing well differentiated and dedifferentiated liposarcomas (WDLS/DDLS) were treated with a selective CDK 4/6 inhi…

Cohorts

Alteration frequency by cohort (28)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

gdcObserved28 cohort rows · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Adrenocortical Carcinoma TCGA-ACC	Adrenal Cortical CarcinomaALIAS

Literature

Linked publications (6)

25 per page, newest first.

pubmedPublishedShowing 1–6 of 6 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.
· J Clin Oncol · 2013 · PMID 23569312 · validated civic_curation pubmed
CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.
· Cancer Cell · 2014 · PMID 25002028 · validated civic_curation pubmed
Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.
· JAMA Oncol · 2016 · PMID 27124835 · validated civic_curation pubmed
Ribociclib, a Cdk4/Cdk6 kinase inhibitor, enhances glucocorticoid sensitivity in B-acute lymphoblastic leukemia (B-All).
· Biochem Pharmacol · 2018 · PMID 29408328 · validated

CDK4 EXPRESSION4
Alpelisib	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	D	Supports Sensitivity Response	4	accepted	EID264 In mouse xenograft studies of PIK3CA mutant breast cancers, the combination of PI3K and CDK4/6 inhibitors overcomes intrinsic and adaptive resistance leading to tumor regressions. PMID 25002028 · Vora et al., 2014 · Open in CIViC	civic
Palbociclib	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	B	Supports Sensitivity Response	3	rejected	EID345 Palbociclib has been shown to dramatically improve progression-free survival by over 18 months in patients with ER+ Breast Cancer. PMID 23898052 · Logan et al., 2013 · Open in CIViC	civic
〃	Sarcoma	Predictive	D	Supports Sensitivity Response	4	accepted	EID4872 A preclinical study to explore the efficacy of CDK4/6 inhibition with palbociclib, in a panel of sarcoma cell lines and sarcoma tumor xenografts (PDXs). The responsiveness of these cell lines correlat… (full text at CIViC) PMID 26528855 · Perez et al., 2015 · Open in CIViC	civic
Dexamethasone + RibociclibCombination	Childhood B-cell Acute Lymphoblastic LeukemiaUNRESOLVED	Predictive	D	Supports Sensitivity Response	2	accepted	EID7798 CDK4 was found to be significantly overexpressed in the bone marrow of MLL-rearranged B-ALL patients (n=70) compared to normal bone marrow (n=74, p<.001). Combination treatment with dexamethasone (glu… (full text at CIViC) PMID 29408328 · Bortolozzi et al., 2018 · Open in CIViC	civic

CDK4 EXPRESSION4

Alpelisib

Estrogen Receptor-positive Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

accepted

EID264

In mouse xenograft studies of PIK3CA mutant breast cancers, the combination of PI3K and CDK4/6 inhibitors overcomes intrinsic and adaptive resistance leading to tumor regressions.

PMID 25002028 · Vora et al., 2014 · Open in CIViC

civic

Palbociclib

Estrogen Receptor-positive Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

rejected

EID345

Palbociclib has been shown to dramatically improve progression-free survival by over 18 months in patients with ER+ Breast Cancer.

PMID 23898052 · Logan et al., 2013 · Open in CIViC

civic

〃

Sarcoma

Predictive

Supports Sensitivity Response

accepted

EID4872

A preclinical study to explore the efficacy of CDK4/6 inhibition with palbociclib, in a panel of sarcoma cell lines and sarcoma tumor xenografts (PDXs). The responsiveness of these cell lines correlat… (full text at CIViC)

PMID 26528855 · Perez et al., 2015 · Open in CIViC

civic

Dexamethasone + RibociclibCombination

Childhood B-cell Acute Lymphoblastic LeukemiaUNRESOLVED

Predictive

Supports Sensitivity Response

accepted

EID7798

CDK4 was found to be significantly overexpressed in the bone marrow of MLL-rearranged B-ALL patients (n=70) compared to normal bone marrow (n=74, p<.001). Combination treatment with dexamethasone (glu… (full text at CIViC)

PMID 29408328 · Bortolozzi et al., 2018 · Open in CIViC

civic

CDK4 Overexpression2
Dexamethasone + RibociclibCombination	Childhood B-cell Acute Lymphoblastic LeukemiaUNRESOLVED	Predictive	D	Supports Sensitivity Response	3	rejected	EID8114 CDK4 was found to be significantly overexpressed in the bone marrow of MLL-rearranged B-ALL patients (n=70) compared to normal bone marrow (n=74, p<.001). Combination treatment with dexamethasone (glu… (full text at CIViC) PMID 29408328 · Bortolozzi et al., 2018 · Open in CIViC	civic
Palbociclib + RibociclibSubstitutes	Alveolar Rhabdomyosarcoma	Predictive	D	Supports Resistance	3	submitted	EID7138 Analysis of the antiproliferative effects of pharmacologic CDK4/6 inhibitors provided initial evidence of this notion, as lowest CDK4- expressing Rh28 cells showed the highest sensitivity to both LEE0… (full text at CIViC) PMID 25810375 · Olanich et al., 2015 · Open in CIViC	civic

CDK4 Overexpression2

Dexamethasone + RibociclibCombination

Childhood B-cell Acute Lymphoblastic LeukemiaUNRESOLVED

Predictive

Supports Sensitivity Response

rejected

EID8114

PMID 29408328 · Bortolozzi et al., 2018 · Open in CIViC

civic

Palbociclib + RibociclibSubstitutes

Alveolar Rhabdomyosarcoma

Predictive

Supports Resistance

submitted

EID7138

Analysis of the antiproliferative effects of pharmacologic CDK4/6 inhibitors provided initial evidence of this notion, as lowest CDK4- expressing Rh28 cells showed the highest sensitivity to both LEE0… (full text at CIViC)

PMID 25810375 · Olanich et al., 2015 · Open in CIViC

civic

CDK4 R24C1
Palbociclib	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	1	accepted	EID1376 In a cohort of 143 patients with primary invasive melanoma, copy-number gain of CDK4 was observed (FISH) in 37% of cases. PD0332991 efficacy (proliferation assay) was assessed in a panel of 47 melanom… (full text at CIViC) PMID 24495407 · Young et al., 2014 · Open in CIViC	civic

CDK4 R24C1

Palbociclib

Cutaneous MelanomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID1376

In a cohort of 143 patients with primary invasive melanoma, copy-number gain of CDK4 was observed (FISH) in 37% of cases. PD0332991 efficacy (proliferation assay) was assessed in a panel of 47 melanom… (full text at CIViC)

PMID 24495407 · Young et al., 2014 · Open in CIViC

civic