CDK4, cyclin dependent kinase 4, 1019

N. diseases: 433; N. variants: 8
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE Compared with having a truncal melanoma, CDK4 (vs. noncarriers: lower extremities OR = 14.5, 95% confidence interval [CI] = 5.02-42.0, P < 0.001; upper extremities OR = 6.88, 95% CI = 2.37-19.9, P < 0.001; head and neck OR = 18.6, 95% CI = 4.04-85.2, P < 0.001) and CDKN2A (vs. noncarriers: lower extremities OR = 3.01, 95% CI = 1.56-5.82, P < 0.05; upper extremities OR = 1.91, 95% CI = 1.03-3.52, P < 0.05; head and neck OR = 5.40, 95% CI = 2.10-13.9, P < 0.001) carriers had higher odds of developing melanoma at all other sites. 31326397 2020
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE To investigate the underlying mechanisms, levels of c-Myc, β-catenin, phosphorylated retinoblastoma (p-Rb), cyclin-dependent kinase 4 (CDK4), and Cyclin D3 proteins were determined by western blotting in melanoma A375 cells with WSB2 knocked down. 31103822 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE We observed that melanoma PDXs resistant to CDK4/6i frequently displayed activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, and inhibition of this pathway improved CDK4/6i response in a p21-dependent manner. 31413145 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma. 31439820 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors. 31320640 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. 31555743 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE We show that the CDK4/6 inhibitor PD0332991 causes a significant decrease in tumor growth in a xenotransplantation mouse model of human melanoma. shRNA knockdown of either CDK4 or CDK6 significantly reduces cell proliferation and impedes their migratory capacity <i>in vitro</i>, which translates into a strong inhibition of tumor growth in xenotransplantation experiments. 30858922 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE Combinatorial inhibition of MEK1/2 and CDK4/6 is currently undergoing clinical investigation in NRAS-mutant melanoma. 30819666 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE Panel screening of 56 other cancer predisposition genes did not reveal other germline pathogenic variants associated with melanoma (CDK4, BAP1, POT1), although pathogenic variants in TP53, CHEK2, and BRCA2 were present in three separate patients and some patients had variants of uncertain significance. 31567591 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE In our study we comprehensively characterized 488 melanoma cases from 451 non-CDKN2A/CDK4 families for mutations in 30 established and candidate melanoma susceptibility genes using a custom-designed targeted gene panel approach. 30414346 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE Besides the identification of well-recognized driver mutations of <i>BRAF</i> (3.1%), <i>RAS</i> family (6.2%), <i>NF1</i> (7.8%), and <i>KIT</i> (23.1%) in MMs, our study also found that (i) mutations and amplifications in the transmembrane nucleoporin gene <i>POM121</i> (30.8%) defined a patient subgroup with higher tumor proliferation rates; (ii) enrichment of structural variations between chromosomes 5 and 12 defined a patient subgroup with significantly worse clinical outcomes; (iii) over 50% of the MM patients harbored recurrent focal amplification of several oncogenes (<i>CDK4, MDM2,</i> and <i>AGAP2</i>) at 12q13-15, and this co-occurred significantly with amplification of <i>TERT</i> at 5p15, which was verified in the validation cohort; (iv) the PDX trial demonstrated robust antitumor effects of palbociclib in MMs harboring <i>CDK4</i> amplification. 30782616 2019
MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 3
0.700 Biomarker disease CLINGEN The interplay of CDK4 and CDK6 in melanoma. 30858922 2019
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by <sup>18</sup>F-FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). 29347968 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE <b/> Dual MAPK and CDK4/6 targeting is an emerging strategy in melanoma, but toxicity and acquired resistance are limitations. 29716938 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE Preclinical studies in cell cultures and mouse models proved that CDK4/6i are active against a broad spectrum of solid tumors other than breast cancer, including liposarcoma, rhabdomyosarcoma, non-small cell lung cancer, glioblastoma multiforme, esophageal cancer, and melanoma. 30631751 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE Increased CDK4 activity occurs in the majority of melanomas and CDK4/6 inhibitors in combination with BRAF and MEK inhibitors are currently in clinical trials for the treatment of melanoma. 29243224 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE We also showed that CDK4/6 blockade resensitized drug resistant melanoma to SOC therapy. 29541385 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE CDK4/6-inhibition represses this program in individual malignant cells, induces senescence, and reduces melanoma tumor outgrowth in mouse models in vivo when given in combination with immunotherapy. 30388455 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. 28870692 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE MEK/CDK4,6 co-targeting is effective in a subset of NRAS, BRAF and 'wild type' melanomas. 30405888 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 AlteredExpression disease BEFREE In vivo study indicated that the silencing of hsa_circ_0025039 inhibits melanoma tumor formation and downregulates miR-198 and CDK4 expression. 30219673 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. 29496664 2018
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE In sum, deregulation of all three PPs appears central to neoplastic progression for melanoma, and the customary reference to the p16<sup>INKA</sup>/CDK4/pRB pathway may no longer be accurate; all PPs are potentially critical targets of CDK-cyclins in melanoma. 28192409 2017
CUI: C0025202
Disease: melanoma
melanoma
0.700 Biomarker disease BEFREE Such senescent cells suppress the antitumor immune response and promote melanoma growth in immunocompetent, <i>in vivo</i> models.<b>Implications:</b> The ability of prolonged CDK4/6 inhibitor treatment to induce cellular senescence and a robust SASP in primary cells may hinder therapeutic efficacy and promote long-term, gerontogenic consequences that should be considered in clinical trials aiming to treat melanoma and other cancer types.<i></i>. 28039358 2017
CUI: C0025202
Disease: melanoma
melanoma
0.700 GeneticVariation disease BEFREE Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. 26999380 2017