Molecular Mechanisms of Tumour Progression and Treatment Response

Molecular Mechanisms of Tumour Progression and Treatment Response group

Led by:
Associate Professor Fred Hollande,
Department of Pathology
+61 3 8559 7023

Fred's research group aims to understand mechanisms that underlie the genetic and non-genetic heterogeneity within individual tumours, and to characterise the role played by this heterogeneity on metastatic progression and treatment response. They also aim to characterise the molecular mechanisms that underlie the phenotypic plasticity of cancer cells, and to understand how this plasticity affects the response of tumour-initiating cells to anti-cancer treatments. Translational objectives of their work include the discovery of novels biomarkers providing early prognosis and prediction of treatment response, and the improvement of therapeutic efficacy by targeting cells that drive recurrence to current treatments.

They do this by combining the phenotypic and genotypic analysis of samples freshly obtained from cancer patients in order to characterise molecular networks that are instrumental for subpopulations of cancer cells to resist current treatments and drive post-treatment relapse. Benefiting from the collaborative efforts of surgeons, medical oncologists, genomics specialists, statisticians and systems biologists from several VCCC member organisations, this project uses an innovative approach to characterise and target these drug-resistant cancer cell subpopulations. To do so, Fred's lab has developed ex vivo models that allow the unbiased analysis of differential responses to drug treatment by individual subpopulations of cancer cells within individual tumours. This will allow the identification of pathways that drive either the intrinsic drug-resistance ability of specific cancer cell subpopulations or the plasticity behaviours that allow them to adapt before dying upon treatment exposure.

Preclinical orthotopic graft models are then used to validate the sensitivity of these newly identified targets to pharmacological inhibition.

A broad array of experimental models are used in the team, including 2D and 3D tissue culture, ex vivo analysis of human tumour samples, live and static cell imaging, flow cytometry, cytotoxicity assays, methylation analysis, genome-wide RNA analysis, xenografted mice models.