Restoring adiponectin signalling to prevent prostate cancer progression

Overview

Advanced prostate cancer (PCa) is a leading cause of cancer-associated death in Australian men. Anti-androgens, which exploit the tumour’s reliance on androgens for its growth and spread, offer temporary remission in advanced PCa patients, but due to treatment resistance, fail to be curative. A further complication of anti-androgens is that they trigger a deleterious suite of metabolic side-effects resembling obesity/Metabolic syndrome. These symptoms not only impact patient health but promote the tumour to be more aggressive and resist treatment. Vital new treatments are therefore required.

Adiponectin is fat-secreted hormone known for its role in insulin sensitisation & metabolism; but its circulating levels are decreased in men with PCa and continue to decrease in men with advanced disease. Our work uncovered that adiponectin’s signalling receptors are also reduced in prostate tumour tissue, are again further decreased in metastatic PCa and are linked to disease recurrence. We therefore devised a completely novel therapeutic strategy, restoring the adiponectin signalling axis, to prevent PCa progression. Using a novel peptide drug to agonise adiponectin signalling, we demonstrated enhanced adiponectin activity significantly inhibited prostate tumour growth, slowed PCa progression to treatment resistance & extended mouse survival.

Research activities

This project aims to determine the impact of our novel adiponectin receptor agonist drug in preclinical models of PCa by: (1) assessing its anti-tumour efficacy, (2) characterising efficacious response in tumours by assessing drug impacts on key cancer hallmarks, and (3) characterising whole-body metabolic response to drug. These objectives are expected to contribute to our industry-partnered development of this novel drug and its future progression to clinical testing.

This project may employ multiple preclinical & molecular techniques to best understand the impact of our novel drug on whole-body phenotype & anti-tumour efficacy. Approaches used could include:

• animal modelling of prostate cancer for preclinical drug testing
• metabolic phenotyping and body composition imaging of mice
• characterisation of tumours in live animals by imaging techniques
• characterisation of drug impacts on tissues through standard molecular techniques (qRT-PCR, Western blot, ELISA, Immunohistochemistry) and multi-omics techniques with subsequent bioinformatic analysis.

Through this project, prospective students will gain skills in numerous scientific techniques that are broadly applicable throughout the biomedical science disciplines. Based at the world-class Translational Research Institute, the student will access the state-of-the-art facilities and join a vibrant team of talented biomedical researchers within the Adipokine research group & broader Australian Prostate Cancer Research Centre – Queensland.

Skills and experience

Eligible candidates considered must have:

• ability to work in a diverse multi-disciplinary team environment
• excellent verbal and written communication skills
• eagerness to take initiative and undertake complex problem-solving activities
• precise accuracy and attention to detail
• skills in planning and prioritising work to meet deadlines
• interest in preclinical animal modelling or in downstream characterisation of animal tissues.

Keywords

• Adipokines
• Prostate Cancer
• Treatment resistance
• Adiponectin
• Leptin
• Novel Drugs
• Preclinical Models

Contact

Please contact Lisa Philp for more information.