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Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines.

Young RJ, Waldeck K, Martin C, Foo JH, Cameron DP, Kirby L, Do H, Mitchell C, Cullinane C, Liu W, Fox SB, Dutton-Regester K, Hayward NK, Jene N, Dobrovic A, Pearson RB, Christensen JG, Randolph S, McArthur GA, Sheppard KE.

Pigment Cell Melanoma Res. 2014 Jul;27(4):590-600. doi: 10.1111/pcmr.12228. Epub 2014 Mar 6.


p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.

Cen L, Carlson BL, Schroeder MA, Ostrem JL, Kitange GJ, Mladek AC, Fink SR, Decker PA, Wu W, Kim JS, Waldman T, Jenkins RB, Sarkaria JN.

Neuro Oncol. 2012 Jul;14(7):870-81. doi: 10.1093/neuonc/nos114. Epub 2012 Jun 18.


PD-0332991, a potent and selective inhibitor of cyclin-dependent kinase 4/6, demonstrates inhibition of proliferation in renal cell carcinoma at nanomolar concentrations and molecular markers predict for sensitivity.

Logan JE, Mostofizadeh N, Desai AJ, VON Euw E, Conklin D, Konkankit V, Hamidi H, Eckardt M, Anderson L, Chen HW, Ginther C, Taschereau E, Bui PH, Christensen JG, Belldegrun AS, Slamon DJ, Kabbinavar FF.

Anticancer Res. 2013 Aug;33(8):2997-3004.


The CDK4/CDK6 inhibitor PD0332991 paradoxically stabilizes activated cyclin D3-CDK4/6 complexes.

Paternot S, Colleoni B, Bisteau X, Roger PP.

Cell Cycle. 2014;13(18):2879-88. doi: 10.4161/15384101.2014.946841.


Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for melanoma.

Mahgoub T, Eustace AJ, Collins DM, Walsh N, O'Donovan N, Crown J.

Int J Oncol. 2015 Sep;47(3):900-8. doi: 10.3892/ijo.2015.3097. Epub 2015 Jul 21.


Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6.

Tang LH, Contractor T, Clausen R, Klimstra DS, Du YC, Allen PJ, Brennan MF, Levine AJ, Harris CR.

Clin Cancer Res. 2012 Sep 1;18(17):4612-20. doi: 10.1158/1078-0432.CCR-11-3264. Epub 2012 Jul 3.


Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway.

von Witzleben A, Goerttler LT, Marienfeld R, Barth H, Lechel A, Mellert K, Böhm M, Kornmann M, Mayer-Steinacker R, von Baer A, Schultheiss M, Flanagan AM, Möller P, Brüderlein S, Barth TF.

Cancer Res. 2015 Sep 15;75(18):3823-31. doi: 10.1158/0008-5472.CAN-14-3270. Epub 2015 Jul 16.


Specific Antileukemic Activity of PD0332991, a CDK4/6 Inhibitor, against Philadelphia Chromosome-Positive Lymphoid Leukemia.

Nemoto A, Saida S, Kato I, Kikuchi J, Furukawa Y, Maeda Y, Akahane K, Honna-Oshiro H, Goi K, Kagami K, Kimura S, Sato Y, Okabe S, Niwa A, Watanabe K, Nakahata T, Heike T, Sugita K, Inukai T.

Mol Cancer Ther. 2016 Jan;15(1):94-105. doi: 10.1158/1535-7163.MCT-14-1065. Epub 2015 Dec 4.


Induction of Therapeutic Senescence in Vemurafenib-Resistant Melanoma by Extended Inhibition of CDK4/6.

Yoshida A, Lee EK, Diehl JA.

Cancer Res. 2016 May 15;76(10):2990-3002. doi: 10.1158/0008-5472.CAN-15-2931. Epub 2016 Mar 17.


Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy.

Roberts PJ, Bisi JE, Strum JC, Combest AJ, Darr DB, Usary JE, Zamboni WC, Wong KK, Perou CM, Sharpless NE.

J Natl Cancer Inst. 2012 Mar 21;104(6):476-87. doi: 10.1093/jnci/djs002. Epub 2012 Feb 1.


Virtually 100% of melanoma cell lines harbor alterations at the DNA level within CDKN2A, CDKN2B, or one of their downstream targets.

Walker GJ, Flores JF, Glendening JM, Lin AH, Markl ID, Fountain JW.

Genes Chromosomes Cancer. 1998 Jun;22(2):157-63. Review.


CDKN2A/p16 Loss Implicates CDK4 as a Therapeutic Target in Imatinib-Resistant Dermatofibrosarcoma Protuberans.

Eilers G, Czaplinski JT, Mayeda M, Bahri N, Tao D, Zhu M, Hornick JL, Lindeman NI, Sicinska E, Wagner AJ, Fletcher JA, Mariño-Enriquez A.

Mol Cancer Ther. 2015 Jun;14(6):1346-53. doi: 10.1158/1535-7163.MCT-14-0793. Epub 2015 Apr 7.


CDK4/6-inhibiting drug substitutes for p21 and p16 in senescence: duration of cell cycle arrest and MTOR activity determine geroconversion.

Leontieva OV, Blagosklonny MV.

Cell Cycle. 2013 Sep 15;12(18):3063-9. doi: 10.4161/cc.26130. Epub 2013 Aug 22.


Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.

Konecny GE, Winterhoff B, Kolarova T, Qi J, Manivong K, Dering J, Yang G, Chalukya M, Wang HJ, Anderson L, Kalli KR, Finn RS, Ginther C, Jones S, Velculescu VE, Riehle D, Cliby WA, Randolph S, Koehler M, Hartmann LC, Slamon DJ.

Clin Cancer Res. 2011 Mar 15;17(6):1591-602. doi: 10.1158/1078-0432.CCR-10-2307. Epub 2011 Jan 28.


CDKN2A and CDK4 mutation analysis in Italian melanoma-prone families: functional characterization of a novel CDKN2A germ line mutation.

Della Torre G, Pasini B, Frigerio S, Donghi R, Rovini D, Delia D, Peters G, Huot TJ, Bianchi-Scarra G, Lantieri F, Rodolfo M, Parmiani G, Pierotti MA.

Br J Cancer. 2001 Sep 14;85(6):836-44.


An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma.

Teh JL, Purwin TJ, Greenawalt EJ, Chervoneva I, Goldberg A, Davies MA, Aplin AE.

Cancer Res. 2016 Sep 15;76(18):5455-66. doi: 10.1158/0008-5472.CAN-15-3384. Epub 2016 Aug 3.


Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A, P14ARF or cdk4 genes.

Soufir N, Bressac-de Paillerets B, Desjardins L, Lévy C, Bombled J, Gorin I, Schlienger P, Stoppa-Lyonnet D.

Br J Cancer. 2000 Feb;82(4):818-22.


CDKN2A/p16 is inactivated in most melanoma cell lines.

Castellano M, Pollock PM, Walters MK, Sparrow LE, Down LM, Gabrielli BG, Parsons PG, Hayward NK.

Cancer Res. 1997 Nov 1;57(21):4868-75.


Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia.

Wang L, Wang J, Blaser BW, Duchemin AM, Kusewitt DF, Liu T, Caligiuri MA, Briesewitz R.

Blood. 2007 Sep 15;110(6):2075-83. Epub 2007 May 30.

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