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

Karen E Sheppard; Shatha AbuHammad

doi:10.1080/23723556.2019.1673643

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

Mol Cell Oncol. 2019 Oct 17;6(6):e1673643. doi: 10.1080/23723556.2019.1673643. eCollection 2019.

Authors

Karen E Sheppard^{1

2}, Shatha AbuHammad¹

Affiliations

¹ Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
² Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.

Abstract

Cyclin-dependent kinase -4 and -6 (CDK4/6) inhibitors are currently being assessed in clinical trials for the treatment of many cancers including melanoma. While investigating the mechanisms of CDK4/6 inhibitor resistance in melanoma, we uncovered a mechanism of action of these inhibitors in regulating the expression of both the mouse double minute 4 (MDM4) oncogene and tumor protein p53 (TP53).

Keywords: CDK4; CDK6; MDM4; PRMT5; TP53; acquired resistance; melanoma; p21; pre-mRNA splicing.

Grants and funding

This work was supported by the Peter MacCallum Cancer Foundation (AU); Cancer Council Victoria (AU) Grant under Grant [1108149]; and National Health and Medical Research Council of Australia under Grant [1042986].