Cyclin-Dependent Kinase 4

Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.

Also Known As:

Cdk4 Cyclin-Dependent Kinase; Cdk4 Protein; Cell Division Protein Kinase 4; Cyclin D-Dependent Kinase CDK4; PSK-J3 Kinase; p34PSK-J3 Kinase; Cdk4 Cyclin Dependent Kinase; Cyclin D Dependent Kinase CDK4; Cyclin Dependent Kinase 4; Cyclin-Dependent Kinase, Cdk4; PSK J3 Kinase; Protein Kinase, Cdk4; p34PSK J3 Kinase; Cdk4 Protein Kinase

Networked: 947 relevant articles (74 outcomes, 119 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Bardia, Aditya: 13 articles (10/2022 - 01/2017)
2.	Rugo, Hope S: 10 articles (01/2022 - 02/2016)
3.	Harbeck, Nadia: 7 articles (01/2022 - 01/2017)
4.	Iwata, Hiroji: 7 articles (01/2022 - 01/2017)
5.	Slamon, Dennis J: 7 articles (01/2021 - 08/2013)
6.	Liu, Zhen: 6 articles (03/2022 - 04/2011)
7.	Toi, Masakazu: 6 articles (12/2021 - 09/2017)
8.	Huang, Xin: 6 articles (08/2021 - 01/2015)
9.	Finn, Richard S: 6 articles (01/2021 - 01/2015)
10.	Turner, Nicholas C: 6 articles (01/2021 - 01/2017)

Related Diseases

1.	Breast Neoplasms (Breast Cancer) 01/01/2023 - "With the continuous development of endocrine targeting drugs, especially the emergence of selective cyclin-dependent kinase (CDK4/6) inhibitors, the overall survival time in patients with HR+HER2- advanced breast cancer has been greatly improved. " 01/01/2021 - "The cyclin-dependent kinase 4/6 inhibitor was also effective for the metastatic breast cancer, and, to date, the patient's disease has remained stable for more than one year. " 12/10/2018 - "Cyclin dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) are effective in breast cancer; however, drug resistance is frequently encountered and poorly understood. " 11/01/2017 - "Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. " 08/16/2021 - "Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. "
2.	Neoplasms (Cancer) 04/01/2021 - "The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR = 0.547, P < 0.001), overall survival (pooled HR= 0.755, P < 0.001), and tumor response rates (ORR, pooled OR= 1.478, P < 0.001; CBR, pooled OR= 1.201, P < 0.001) with manageable toxicities (pooled OR= 3.280, P < 0.001). " 07/18/2023 - "Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology for Cancer Patients" International Study." 01/29/2021 - "Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are being tested in numerous clinical trials and are currently employed successfully in the clinic for the treatment of breast cancers. " 10/15/2020 - "Alterations in this pathway are found in most human cancers, and specific cyclin-dependent kinase Cdk4/6 inhibitors are approved or in clinical trials for the treatment of diverse cancers. " 09/01/1997 - "The aim of the present study was to determine whether genetic alterations of p16INK4 (MTS1) and/or cyclin-dependent kinase 4 (CDK4) occur in the genesis of these tumors. "
3.	Retinoblastoma (Glioblastoma, Retinal) 01/01/2022 - "Further mechanism studies revealed that p16ink4a affected the expression level of cyclin-dependent kinase 4 (CDK4) and phosphorylation of retinoblastoma (pRb), which could be a potential pathway in regulating cardiac remodeling after MI. " 01/01/2019 - "WGA and SBA reduced levels of B cell lymphoma-2 (Bcl-2), phosphorylation of Bcl-2-associated death promoter (Bad), cyclin-dependent kinase 4 (Cdk4), and phosphorylation of the retinoblastoma (Rb). " 03/01/2018 - "Our data further indicated that Cdc37 increased the stability of cyclin-dependent kinase 4 (CDK4) to activate the retinoblastoma 1 (RB1) signaling pathway, followed by increased expression of Bcl-2 and Bcl-xL, which ultimately promoted cell survival in CRC. " 11/01/1999 - "In contrast, the expressions of other cell cycle regulated genes and proto-oncogene, including the cyclin-dependent kinase 4 (cdk4), retinoblastoma, p16INK4a and p21H-ras, were not altered. " 06/15/1997 - "In the present study, we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in cyclin-dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using molecular biology techniques. "
4.	Brain Neoplasms (Brain Tumor) 11/01/2015 - "Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model." 10/15/2020 - "In cohort D (n = 9), unbound brain metastases concentrations of total active abemaciclib analytes were 96- [cyclin-dependent kinase 4 (CDK4)] and 19-fold (CDK6) above in vitro IC50. " 01/01/1998 - "We have measured the gene dosage of the epidermal growth factor receptor (EGFR), mouse double minute 2 (MDM2), and cyclin-dependent kinase 4 (CDK4) genes in a series of brain tumor specimens and correlated their amplification status with standard prognostic factors and survival. " 01/01/2023 - "Palbociclib, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has shown promise in phase I clinical trials of pediatric patients with progressive/refractory brain tumors using the oral administration route; however, pharmacokinetic limitations and toxicity issues remain. " 01/01/2021 - "The aim of this study was to determine the maximum tolerated dose (MTD) and describe toxicities related to palbociclib, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in pediatric patients with progressive/refractory brain tumors with intact retinoblastoma protein. "
5.	Melanoma (Melanoma, Malignant) 12/01/2021 - "Targeting cyclin-dependent kinase 4/6 as a therapeutic approach for mucosal melanoma." 01/01/2019 - "Increased CDK4 protein expression predicts a poor prognosis in mucosal melanoma associated with the p16INK4a-CDK4-pRb pathway." 09/01/2015 - "A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. " 07/15/2008 - "Here, we used a genomic strategy to define a novel group of melanoma cell lines with co-overexpression of cyclin-dependent kinase 4 (CDK4) and KIT. " 03/01/2006 - "We primarily used a unique Utah genealogical resource to identify independent melanoma prone families whom we tested for mutations in CDKN2A, cyclin-dependent kinase 4, and alternate reading frame. "

Related Drugs and Biologics

1.	Hormones (Hormone)
2.	ErbB Receptors (EGF Receptor)
3.	palbociclib
4.	ribociclib
5.	abemaciclib
6.	Letrozole (Femara)
7.	Estrogen Receptors
8.	Fulvestrant (Faslodex)
9.	Aromatase Inhibitors
10.	human ERBB2 protein

Related Therapies and Procedures

1.	Therapeutics
2.	Oral Administration
3.	Drug Therapy (Chemotherapy)
4.	Immunotherapy
5.	Aftercare (After-Treatment)