Melbourne Medical School Collected Works - Research Publications

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Author: McArthur, Grant × Author: Sheppard, Karen × End date: 2020 × Start date: 2020 × Type: Journal Article ×

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    Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAFV600 melanoma cells
    Smith, LK ; Parmenter, T ; Gould, CM ; Madhamshettiwar, PB ; Sheppard, KE ; Simpson, KJ ; McArthur, GA (NATURE RESEARCH, 2020-10-12)
    Identification of mechanisms underlying sensitivity and response to targeted therapies, such as the BRAF inhibitor vemurafenib, is critical in order to improve efficacy of these therapies in the clinic and delay onset of resistance. Glycolysis has emerged as a key feature of the BRAF inhibitor response in melanoma cells, and importantly, the metabolic response to vemurafenib in melanoma patients can predict patient outcome. Here, we present a multiparameter genome-wide siRNA screening dataset of genes that when depleted improve the viability and glycolytic response to vemurafenib in BRAFV600 mutated melanoma cells. These datasets are suitable for analysis of genes involved in cell viability and glycolysis in steady state conditions and following treatment with vemurafenib, as well as computational approaches to identify gene regulatory networks that mediate response to BRAF inhibition in melanoma.
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    Obesity and the Impact on Cutaneous Melanoma: Friend or Foe?
    Smith, LK ; Arabi, S ; Lelliott, EJ ; McArthur, GA ; Sheppard, KE (MDPI, 2020-06)
    Excess body weight has been identified as a risk factor for many types of cancers, and for the majority of cancers, it is associated with poor outcomes. In contrast, there are cancers in which obesity is associated with favorable outcomes and this has been termed the "obesity paradox". In melanoma, the connection between obesity and the increased incidence is not as strong as for other cancer types with some but not all studies showing an association. However, several recent studies have indicated that increased body mass index (BMI) improves survival outcomes in targeted and immune therapy treated melanoma patients. The mechanisms underlying how obesity leads to changes in therapeutic outcomes are not completely understood. This review discusses the current evidence implicating obesity in melanoma progression and patient response to targeted and immunotherapy, and discusses potential mechanisms underpinning these associations.