Journal article

CDK4/6 Inhibition Reprograms Mitochondrial Metabolism in BRAF(V600) Melanoma via a p53 Dependent Pathway

Nancy T Santiappillai, Shatha Abuhammad, Alison Slater, Laura Kirby, Grant A McArthur, Karen E Sheppard, Lorey K Smith

CANCERS | MDPI | Published : 2021

Abstract

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. Understanding their mechanism of action and interaction with other therapies is vital in their clinical development. CDK4/6 regulate the cell cycle via phosphorylation and inhibition of the tumour suppressor RB, and in addition can phosphorylate many cellular proteins and modulate numerous cellular functions including cell metabolism. Metabolic reprogramming is observed in melanoma following standard-of-care BRAF/MEK inhibition and is involved in both therapeutic response and resistance. In preclinical mode..

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Grants

Awarded by National Health and Medical Research Council


Awarded by Cancer Council Victoria


Funding Acknowledgements

This research was funded by National Health and Medical Research Council grant number 1175894 and Cancer Council Victoria grant number 1108149.