Melanoma Cell Biology
Project 1: Explore the utility of circulating DNA/RNA in monitoring tumour burden and response to therapy
Circulating tumour DNA is associated with tumour burden and melanoma patients with low baseline ctDNA have better response and longer progression-free survival. Moreover, a fall in ctDNA during treatment is an independent predictor of response to BRAF inhibitors in melanoma. The sensitivity and specificity of circulation tumour markers, including RNA and methylated tumour DNA, as well as tumour markers contained within circulating exosomes, will be evaluated during this project.
Project 2: Examine effectors that modulate response of melanoma to molecular targeted therapies
Drugs targeting mitogen activated protein kinase (MAPK) signalling, cell cycle regulatory and protein kinase C pathways have shown significant activity in melanoma. Despite the dramatic clinical activity not all patients respond and many patients will acquire resistance to therapy. This project will explore the effectors that modulate response and resistance to molecular targeted therapies in melanoma.
Project 3: Examine the role of the tumour/immune microenvironment on melanoma response to targeted therapy
The PD1 inhibitors, nivolumab and pembrolizumab, show marked anti-tumour activity and have rapidly become the standard first-line immunotherapy for patients with advanced melanoma. The drugs are limited, however, by primary resistance in 20-30% of treated patients. Of those who do respond, only 13.5% develop complete remission, and tumour progression occurs in more than 30% of these patients within 2 years. This project examines the role of melanoma-intrinsic signalling in acquired PD1 inhibitor resistance.