Overcoming therapy induced reprogramming of metabolism in melanoma

Therapies that target oncogenes in cancer have revolutionised cancer care. The major benefits of targeted therapies are high response rates and manageable toxicities, however they do not result in cures in the vast majority of patients. Clinical outcomes of these therapies are limited by cellular adaptation and drug tolerance that allows persistence of residual disease that ultimately results in relapse. This project will take a new approach to address this problem by understanding how cancer cells adapt to targeted therapy, prior to development of overt drug resistance.

Cellular adaptation induced by targeted therapy is characterised by oncogenic network rewiring following initial pathway inhibition. In both preclinical and clinical studies of melanoma, drug induced adaptation reprograms metabolism however whether this creates unique metabolic liabilities that can be targeted to prevent resistance, and the underlying mechanisms that control it, are unknown. We hypothesise that targeting metabolic alterations underlying cancer cell plasticity in response to targeted therapy will offer new opportunities to treat minimal residual disease to improve response and delay or prevent resistance. This project will investigate mechanisms underlying drug-induced cellular adaptation with a focus on metabolism, using MAPK targeted therapy in melanoma as a paradigm.


The McArthur lab investigates oncogenes as therapeutic targets for cancer.
By targeting oncogenic signalling in cancer and understanding the impact of this therapy on both the tumour cell and its microenvironment, we aim to develop novel treatment strategies that are durable and prevent therapy resistance. The McArthur laboratory has a specific interest in melanoma, but also investigates ovarian, lung, colorectal and haematological cancers.
https://www.petermac.org/research/labs/grant-mcarthur-0

Peter MacCallum Cancer Centre in Melbourne Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
https://www.petermac.org/education/research-education

All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program