Target Discovery (CI: Greg Goodall)
Integrate data from diverse EMP studies and screens to identify candidate, EMP-related therapeutic targets, then prioritise candidates and choose validated candidates for progression into Pre-clinical Validation.
Pre-clinical Validation (CI: Robin Anderson)
Assess validated candidates from Target Discovery in established and newly developed models of breast cancer metastasis, dormancy and recurrence, to ensure that candidates to be progressed into Drug Discovery have significant bioactivity in vivo. Will also support the screening of new agents arising from bioinformatically-derived drug leads and analysis of candidate targets and putative drugs in the CTx pipeline.
Clinical Validation (CI: Christobel Saunders)
Validate the differential expression and/or localisation of candidates from Target Discovery in primary tumours, lymph nodes, local recurrences, distant metastases, CTC and DTC.
Mechanisms (CI: Alpha Yap)
Characterise the roles of candidates selected for Drug Discovery in E-cadherin regulation and function and establish the molecular mechanisms associated with their role in EMP, to support the development of assays for the high throughput chemical screens in Drug Discovery.
Drug Discovery (CI: Ian Street)
Identify new drug leads against novel EMP-related targets by employing high throughput chemical screens to identify inhibitors of fully validated candidates from Target Discovery. This will complement the analyses of bioinformatically-derived drug leads, candidate targets and putative drugs in the CTx pipeline.
Diagnostics (CI: Alex Dobrovic)
Assess all prioritised candidates from Drug Discovery in a validated cohort of archival breast cancer specimens using a highly sensitive MT-PCR-based assay optimised for formalin-fixed paraffin-embedded tissues, and develop an assay with prognostic and/or predictive power for clinical development.
Clinical Trial (CI: Anthony Dowling)
Conduct a pilot assessment of CTC and DTC in breast cancer patients undergoing adjuvant therapy in Melbourne and Perth at diagnosis and during follow-up. Subsequent analyses will be combined with ongoing trials in breast cancer patients, coordinated by the Australia New Zealand Breast Cancer Trials Group (ANZBCTG).
