Pre Clinical Research

What do men do if they are deemed ineligible for the PSMA treatments available through ProsTIC?

The research teams at ProsTIC are tackling this question, with innovative pre-clinical research programs in several areas.

At ProsTIC, we brought together world-class researchers in prostate cancer and immunotherapy, to establish evidence that immunotherapy can be effective in treating prostate cancer. The cancer researchers have established human prostate tumours so that they grow in the laboratory outside the patient and have tested an immunotherapy product known as ‘CAR T cell therapy’ that has already been approved by regulatory authorities in Australia

Our results show that CAR T cell therapy eradicates tumours from some patients and are beginning to understand which subtype of prostate tumour will be most responsive. This is important information as we are poised to go to the clinic, and test this new immunotherapy on patients in clinical trials; but it is always better if we can identify the patients most likely to respond.

There is an overwhelming sense of excitement and urgency in this project as we have an approved therapy that can move into clinical trial in a very short time.

Watch this space! Now watch this video of a tumour being killed by CAR-T cells.  This video was created by our talented young research team.

CAR-T Researchers

Dr Laura Porter
Monash Biomedicine Discovery Institute

Dr Joe Zhu
Peter MacCallum Cancer Centre

Dr Natalie Lister
Monash Biomedicine Discovery Institute

Professor Phil Darcy
Peter MacCallum Cancer Centre

Associate Professor Renea Taylor
Monash Biomedicine Discovery Institute
Peter MacCallum Cancer Centre

Associate Professor Paul Neeson
Peter MacCallum Cancer Centre

Professor Gail Risbridger
Monash Biomedicine Discovery Institute
Peter MacCallum Cancer Centre

Professor Joe Trapani
Peter MacCallum Cancer Centre

Theranostic treatment for prostate cancer involves using a radioactive molecule to reveal the cancer’s spread via a positron emission tomography (PET) scan and then a similar radioactive molecule to kill the cancer cells. We have identified new potential targets which could be used to treat advanced metastatic prostate cancer. In this project we plan to design small peptide which specifically bind to the novel targets with high affinity.

Researchers

Dr Luc Furic 
Peter MacCallum Cancer Centre

Dr Mo Haskali
Peter MacCallum Cancer Centre

Biomarker identification in lutetium PSMA-treated prostate cancer patients using circulating tumour DNA 

Prostate-specific membrane antigen (PSMA) is a type 2 membrane glycoprotein overexpressed on prostate cancer cells that has emerged as a key therapeutic target in metastatic castration-resistant prostate cancer (mCRPC). Two landmark trials (including one led by Peter MacCallum Cancer Centre) have positioned lutetium PSMA radionuclide therapy (Lu-PSMA) as a highly effective new treatment option for mCRPC. Nevertheless, responses to Lu-PSMA treatment can be variable, and development of resistance remains inevitable. Identifying biomarkers linked to outcomes with Lu-PSMA is therefore a critical unmet need, in order to select patients most likely to benefit from treatment and to dissect mechanisms of therapeutic resistance.
As part of the newly opened Prostate Imaging and Theranostic Centre of Excellence (ProsTIC), we are running a series of investigator-led clinical trials with Lu-PSMA and other theranostics. Serial plasma samples collected as part of these trials represents a valuable world-first repository of biospecimens with which to perform biomarker discovery. ​With our bespoke prostate cancer cell-free DNA assay that was developed in-house, we are in the ideal position to identify blood-based biomarkers that can be incorporated into future clinical trials.

Researchers

Prof. Michael Hofman
Peter MacCallum Cancer Centre

A/Prof. Arun Azad
Peter MacCallum Cancer Centre

Dr Heidi Fettke
Peter MacCallum Cancer Centre

Cancer is characterised by aberrant cell proliferation and survival. A key requirement for neoplastic growth is increased protein synthesis (mRNA translation). Dysregulation of mRNA translation is common in cancer and multiple oncogenes (e.g. MYC, RAS and PI3KCA) and tumour suppressors (e.g. PTEN, LKB1, TSC1/2 and p53) impinge on the translation apparatus. Efficiency of translation is determined by cis- (e.g. 5’ and 3’ untranslated regions (UTR), upstream open reading frames (uORFs), codon composition) or trans-acting factors (e.g. initiation factors, elongation factors, transfer RNA (tRNA)). In addition to global increase in protein synthesis, cancer cells translate subsets of mRNAs with altered efficiency as compared to normal cells. Recent studies, including our work, suggest posttranscriptional enzymatic modifications on specific tRNA nucleosides as required for proliferation in cancer cells. tRNAs can undergo enzymatic modifications at multiple positions, but modifications of the first base of the anticodon (position U34) by a group of enzymes (ALKBH8, CTU1/2 and the ELP complex) can have drastic impact on translation efficiency. We hypothesise that alterations in U34 tRNA modifications orchestrate the translational reprogramming required for cancer progression and inhibition of U34 modifying enzymes is a new therapeutic avenue in prostate cancer.

Researchers

Dr Luc Furic 
Peter MacCallum Cancer Centre