Peter Mac researchers awarded coveted PCF Challenge Award
28 March 2024
Two Peter Mac researchers will lead an international team to find better outcomes for prostate cancer patients after being awarded a highly competitive USD $1 million Prostate Cancer Foundation (PCF) Challenge Award.
The research, led by Associate Professor Shahneen Sandhu and Professor Belinda Parker, aims to identify which patients with metastatic castration resistant prostate cancer (mCRPC) will most benefit from treatment with 177Lu-PSMA (a form of radiation) and the drug olaparib.
The grant will allow them to use novel imaging, genomic and immune biomarkers to measure the effectiveness of the treatment in this patient group. Associate Professor Sandhu said the team will also define the biological impacts of this combination, which will help to refine how best to use these treatments for maximum effect.
“The rationale for this trial is based on knowledge that Lu-PSMA delivers DNA-damaging radiation to tumour cells, while olaparib prevents DNA repair,” she said.
“Combining these may deliver therapeutic synergy, as tumour cells that receive extensive DNA damage but cannot repair it are more likely to die.
“We will use patient samples and clinical data from the LuPARP trial to define imaging and molecular biomarkers that predict response versus resistance to Lu-PSMA and olaparib, and to understand the mechanisms of action of this treatment.”
Lu-PSMA has been established as standard therapy for mCRPC following a significant survival benefit observed in the phase III VISION trial. Lu-PSMA-based combination therapy is an area of intense interest given the underlying DNA-damaging and immune modulating effects of radioligand therapy and the possibility of therapy synergy.
The PCF-funded phase 1b LuPARP trial (NCT03874884), combining Lu-PSMA with olaparib in patients with mCRPC, translates this hypothesised synergy to the clinical context.
Professor Parker said that this work will likely uncover mechanisms of resistance and opportunities to expand patient response to such therapies in the future.
“We will characterise the immune and genomic landscape and its modulation by Lu-PSMA plus olaparib by leveraging baseline, on-treatment and progressive imaging, tumour and blood samples from the LuPARP trial,” she said.
“Data generated from this research will help to select patients who will most benefit from this treatment option.”
Peter Mac is also collaborating on a project awarded funding by PCF with researchers from the Vancouver Prostate Centre. Associate Professor Arun Azad and Professor Michael Hofman are among the principal investigators to identify new drivers of treatment resistance and provide new biomarkers to help guide treatment selection for patients with mCRPC, reducing the use of futile therapy, and improving quality and length of life.
You can read full details on each project on the PCF website.