Study level
- Master of Philosophy
- Honours
Faculty/School
Faculty of Health
Topic status
We're looking for students to study this topic.
Supervisors
- Position
- Senior Research Fellow
- Division / Faculty
- Faculty of Health
- Position
- Professor
- Division / Faculty
- Faculty of Health
Overview
In advanced PCa, where the cancer has spread into the bone and other organs, the emergence of treatment resistance remains inevitable. For decades the primary form of treatment in advanced PCa has been to target the production and actions of male sex hormones, androgens, the primary developmental and survival factor of prostate tissue. While these therapies result in tumour regression and cancer control, this is temporary and treatment resistance occurs, referred to as castrate resistant prostate cancer (CRPC). In the past decade, new potent androgen-targeted therapies (ATTs) have been developed and are being introduced earlier into the clinical management of advanced PCa. The sequential and prolonged use of new potent ATT agents is allowing men to live longer with PCa, but is shifting the natural history of disease. Prolonged treatment with increasingly potent ATTs in CRPC activates pathways that ultimately drive treatment resistance and can promote altered phenotypic states of differentiation. Recent reports provide strong evidence that in 30% of mCRPC patients, some or all metastases will display characteristics of highly-aggressive treatment-induced phenotypes, broadly referred to as ‘poorly differentiated’ or ‘anaplastic’. The presence of anaplastic metastases alters the survival trajectory of the CRPC patients leading rapidly to mortality and currently lacking any durably effective therapeutics.
Our team has discovered a novel protein complex to be overexpressed in anaplastic mCRPC phenotypes. We have strong evidence that the inhibition of this protein complex using a new class of drugs, can slow down the growth and progression of these tumours. In studies proposed herein, we will undertake studies to inhibit the function of this novel protein complex in anaplastic PCa models and its effects on cancer cell growth, survival and resistance to ATTs.
Approaches/skills and techniques
- Human cancer cell culture;
- Patient-derived organoid culture;
- Molecular biology techniques (DNA/RNA/protein isolation; qRT-PCR; Western blotting; RNA-sequencing)
- In vitro functional assays (Cell growth/proliferation; survival; apoptosis; migration/invasion; drug resistance assays);
- In vivo human xenograft studies in mice (cell line and patient-derived);
- Bioinformatics/computational biology;
- Statistical and data analysis techniques.
Outcomes
The identification of a new treatment for aggressive treatment resistant forms of anaplastic PCa. This would be the first targeted therapy available for men who suffer from this lethal form of PCa.
Required skills and experience
Potential students should have a keen interest in cancer biology and demonstrate a high level of organisation, attention to detail and ability to work in a team environment.