Australian Japan Foundation - VCCC (Hollande)

A/Prof Frederic Hollande from the Department of Pathology, The University of Melbourne, Victorian Comprehensive Cancer Centre (VCCC, VIC) received two cell lines which were funded under the Australia-Japan foundation initiative for his work in intra-tumour heterogeneity and molecular pathways characterisation in various cancers, to understand tumour progression and drug sensitivity. He described his research below.

“Intra-tumour heterogeneity represents a major roadblock to treatment in multiple solid tumours such as colorectal, breast, pancreatic or prostate cancers. Different cell subpopulations within individual tumours exhibit heterogeneous drug sensitivity profiles, due to their different genetic and phenotypic features, and profiling based on the analysis of bulk tumours can hardly predict the behaviour of individual drug-resistant cell subpopulations. Improving our understanding of how different cell subtypes within tumours contribute to tumour progression and treatment response, will allow the development of drugs that more specifically target cells that resist current treatments.

Our team develops a range of approaches to monitor intra-tumour heterogeneity ex-vivo or in-vivo and to characterise the molecular pathways that underpin the behaviour of drug-resistant subpopulations. Once some of these pathways have been identified we screen drug-resistant cell subpopulations for their sensitivity to pathway specific compounds or to compounds that can re-sensitize these cells to immunotherapy.

Cells provided to us under through the Australia-Japan Foundation initiative will be used for the in vivo validation of these findings. To do so they will be injected in immune-competent (Colon26-Luc) or immune-compromised (KP-L3-Luc) animals to validate whether identified genes and targets of interest are indeed essential to tumour progression and treatment response, for example in combination therapy regimen with current standard-of-care compounds.”

"Japan-derived cell-lines for Australia-based preclinical Non-Communicable Disease (NCD) research” is supported by the Australian Government through the Australia-Japan Foundation of the Department of Foreign Affairs and Trade.