Dr Olivia Rossanese, Target Evaluation and Molecular Therapeutics Team
The Target Evaluation and Molecular Therapeutics Team works within the multidisciplinary environment of the Division of Cancer Therapeutics to identify novel targets for drug discovery and to support the discovery of new small-molecule therapeutics to inhibit these targets. The focus of its research is not only the discovery of potent and efficacious drug candidates, but also on gaining an understanding of the underlying target biology and the mechanisms of compound action that lead to efficacy in cell and tumour models. Often, a complete understanding of the therapeutic relevance of target inhibition is not possible without a small-molecule inhibitor, but an exploration of the fundamental target biology can also lead to a better strategy for the design and implementation of targeted therapies.
To achieve these interrelated aims, the team develops and conducts mechanistic and functional cell-based assays to test newly synthesised small molecules and drive decision making in chemistry. Examples of this include assays to measure cell proliferation and viability, anchorage-independent growth, kinase activity, migration, apoptosis and signalling, using a number of readouts and detection systems. Assays must accurately reflect target biology and promote an understanding of the specific molecular consequences of target inhibition and how this contributes to the larger implications of oncogenesis. In parallel, the team is engaged in efforts to validate novel targets, investigate the mechanisms of compound action, and identify suitable cancer cell lines and tumour types for testing targeted therapies. The team uses all these data to develop testable hypotheses regarding predictors of resistance and response to targeted agents, which may be relevant in generating patient selection criteria and a clinical plan.