Journal article

Immunomodulatory Effects of BRAF, MEK, and CDK4/6 Inhibitors: Implications for Combining Targeted Therapy and Immune Checkpoint Blockade for the Treatment of Melanoma

Emily J Lelliott, Grant A McArthur, Jane Oliaro, Karen E Sheppard



The recent advent of targeted and immune-based therapies has revolutionized the treatment of melanoma and transformed outcomes for patients with metastatic disease. The majority of patients develop resistance to the current standard-of-care targeted therapy, dual BRAF and MEK inhibition, prompting evaluation of a new combination incorporating a CDK4/6 inhibitor. Based on promising preclinical data, combined BRAF, MEK and CDK4/6 inhibition has recently entered clinical trials for the treatment of BRAFV600 melanoma. Interestingly, while BRAF- and MEK-targeted therapy was initially developed on the basis of potent tumor-intrinsic effects, it was later discovered to have significant immune-poten..

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Awarded by National Health and Medical Research Council (NHMRC)

Awarded by National Breast Cancer Foundation

Awarded by Melbourne University Research Scholarship

Funding Acknowledgements

This research was supported by the Peter MacCallum Cancer Foundation and grants from National Health and Medical Research Council (NHMRC) to GM & KS (1100189, 1175894) and JO (1139626); National Breast Cancer Foundation grant to JO (IIRS-18-151); Peter Mac Postgraduate Scholarship, Melbourne University Research Scholarship (58616) and Cancer Therapeutics CRC PhD Top Up Scholarship to EL.