A team of Australian researchers, led by Peter Mac’s Dr Shahneen Sandhu, has been awarded a $1M “Challenge Award” from the US’ Prostate Cancer Foundation to undertake a first-in-field trial for a novel combination of radionucleic therapy and a targeted agent in men with aggressive prostate cancer.

The award, announced at the 24th Annual PCF Scientific Retreat (October 5 - 7), was one of only eight successful grants chosen from a pool of 92 international applications.

The PCF’s Challenge Award grants support international, cross-disciplinary teams of investigators conducting pioneering research into critical, unmet medical needs in areas that have the highest potential for impacting and extending lives of men with advanced prostate cancer.

More than 16,000 Australian men are diagnosed with prostate cancer every year, and new therapies are urgently needed for patients with advanced prostate cancer that is no longer responding to standard therapies.

The trial will build on a successful pilot study of 177Lu-PSMA therapy for advanced prostate cancer, conducted at Peter Mac. This involves binding a radioactive particle (Lutetium-177) to a protein (prostate specific membrane antigen or PSMA) that is known to be highly expressed on the surface of prostate cancer and so deliver a toxic payload directly to tumour cells.

“This form of delivery of radiotherapy permits tumour specific killing while minimising the risk of damaging surrounding normal tissues,” said Dr Sandhu, clinician researcher and medical oncologist at Peter Mac.

The researchers will test whether the anti-cancer effectiveness of 177Lu-PSMA therapy can be further improved through combined use of a targeted agent called a PARP-inhibitor, which prevents cancer cells from repairing their DNA.

“Radiation therapy kills cancer cells by damaging the DNA. We predict that the combination of radiotherapy and PARP-inhibitors will more effectively kill cancer cells by preventing DNA repair after radiation-induced DNA damage,” Dr Sandhu says.

The team will conduct a phase I clinical trial to test the efficacy and safety of combining 177Lu-PSMA with the PARP-inhibitor olaparib, and to study the effect of this approach on the immune system. They also aim to identify markers that predict whether a tumour is likely to respond, or become resistant, to this combination of treatments.

The project will be led by researchers at Peter Mac and brings together collaborators from the Chris O'Brien Lifehouse, St Vincent’s Hospital, Box Hill Hospital, and Monash Medical Centre.

 “We are proud and excited to fund these teams who will be conducting life-saving research for patients with prostate cancer,” said Jonathan W. Simons, MD, president and chief executive officer, PCF. “The research conducted by these teams will change the face of how we view the treatment landscape of prostate cancer and have the potential to result in cures even for men with very advanced disease who previously had no further treatment options available.”