Targeting CDK4 in Melanoma

Grant number: 1042986 | Funding period: 2013 - 2015

Completed

Abstract

Major progress has been made in the treatment of cancer by the development of inhibitors of oncogenes that drive cancer growth. This application will test whether this approach can be used for melanomas with activation of the CDK4 oncogene that becomes activated in over 50% of melanomas. We will indentify which patients melanomas respond best to this approach and understand why some melanomas but not other responds providing the scientific framework for clinical trials of CDK4 inhibitors.

Related publications (6)

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CDK4/6 inhibition in cancer: the cell cycle splicing connection

Karen E Sheppard, Shatha AbuHammad

2019-10-18

Cyclin-dependent kinase -4 and -6 (CDK4/6) inhibitors are currently being assessed in clinical trials for the treatment of many ca..

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Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

Shatha AbuHammad, Carleen Cullinane, Claire Martin, Zoe Bacolas, Teresa Ward, Huiqin Chen, Alison Slater, Kerry Ardley, Laura Kirby, Keefe T Chan, Natalie Brajanovski, Lorey K Smith, Aparna D Rao, Emily J Lelliott, Margarete Kleinschmidt, Ismael A Vergara, Anthony T Papenfuss, Peter Lau, Prerana Ghosh, Sue Haupt

2019-09-03

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and are c..

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Palbociclib synergizes with BRAF and MEK inhibitors in treatment naive melanoma but not after the development of BRAF inhibitor resistance

Claire A Martin, Carleen Cullinane, Laura Kirby, Shatha Abuhammad, Emily J Lelliott, Kelly Waldeck, Richard J Young, Natalie Brajanovski, Donald P Cameron, Rachael Walker, Elaine Sanij, Gretchen Poortinga, Ross D Hannan, Richard B Pearson, Rodney J Hicks, Grant A McArthur, Karen E Sheppard

2018-05-15

Increased CDK4 activity occurs in the majority of melanomas and CDK4/6 inhibitors in combination with BRAF and MEK inhibitors are ..

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Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma

SQ Wong, A Behren, VJ Mar, K Woods, J Li, C Martin, KE Sheppard, R Wolfe, J Kelly, J Cebon, A Dobrovic, GA McArthur

2015-01-01

Melanoma is often caused by mutations due to exposure to ultraviolet radiation. This study reports a recurrent somatic C > T chang..

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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

Richard J Young, Kelly Waldeck, Claire Martin, Jung H Foo, Donald P Cameron, Laura Kirby, Hongdo Do, Catherine Mitchell, Carleen Cullinane, Wendy Liu, Stephen B Fox, Ken Dutton-Regester, Nicholas K Hayward, Nicholas Jene, Alexander Dobrovic, Richard B Pearson, James G Christensen, Sophia Randolph, Grant A McArthur, Karen E Sheppard

2014-07-01

We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic tar..

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The Cell-Cycle Regulator CDK4: An Emerging Therapeutic Target in Melanoma

Karen E Sheppard, Grant A McArthur

2013-10-01

The recent clinical success of targeted therapies in melanoma directed at the oncogene BRAF validates the concept of targeting onc..

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