Anti-androgen therapy is commonly used to treat patients with advanced prostate cancer at stages where the disease has spread to the bones. However, new research reveals that anti-androgen treatment can actually facilitate prostate cancer cells to adapt and grow in the bone tumor microenvironment model.
Nathalie Bock, PhD, a senior research fellow at the Queensland University of Technology Centre for Biomedical Technologies, has focused her research on bone metastases from breast and prostate cancers. She developed 3-D miniature bone-like tissue models in which 3-D printed biomimetic scaffolds are seeded with patient-derived bone cells and tumor cells to be used as clinical and preclinical drug testing tools.
The research team investigated their hypothesis that traditional anti-androgen therapy had limited effect in the microenvironment of prostate cancer bone tumors. The team's findings were published in Science Advances (2021; doi: 10.1126/sciadv.abg2564).
"We wanted to see if the therapy could be a contributor of cancer cells' adaptive responses that fueled bone metastasis," noted Dietmar Hutmacher, PhD, a Distinguished Professor at Queensland University of Technology and Bock's mentor. "We developed an all-human, microtissue-engineered model of metastatic tissue using human bone-forming cells, prostate cancer cells, and 3-D printing."
Judith Clements, PhD, a cancer biologist and Distinguished Professor at Queensland University of Technology, said the team bioengineered the microenvironment of a bone tumor to assess the effects of two clinically routinely used anti-androgen therapies-enzalutamide and bicalutamide-on the tumor cells.
"We found that the interactions between the cancer cells, the bone, and the anti-androgens significantly impacted the progress of cancer in the mineralized microenvironment of bone tumors," Clements stated. "This means that the efficacy of these therapies is compromised in the presence of the bone microenvironment."
Hutmacher said an important outcome of the study was the need to upscale the bone tumor microenvironment model platform and make it available to other research groups. "This would enable the prostate cancer research community to develop therapies for a more effective treatment of advanced prostate cancer."
In the future, Bock will use her model with patient-derived cells from patients undergoing prostatectomy, so that it could be used as a personalized preclinical diagnostic and drug testing tool.
"By screening existing and novel drugs using the bone tumor model in the laboratory, doctors will be able to treat individual patients with an anti-cancer therapy that can best suit their clinical need," she explained. "This has the potential to considerably improve the quality of life of patients, because patients will not have to trial a succession of drugs, each of which carry the potential of severe side effects, and which may not work for them."
Jeff Dunn AO, Professor and CEO of the Prostate Cancer Foundation of Australia, said the findings were significant. "This is an important discovery that will help us to better target treatments for men with different types of prostate cancer," he said. "The findings also demonstrate the importance of ongoing research to improve our understanding of how different treatments impact disease progression and spread."
New Concept Drug Hunts Down Late-Stage Prostate Cancer
A new class of drug successfully targets treatment-resistant prostate cancers and prolongs the life of patients. The treatment delivers beta radiation directly to tumor cells, is well-tolerated by patients, and keeps them alive for longer than standard care, according to a Phase III trial presented at the 2021 European Association of Urology Congress.
Despite progress in medicine in recent years, metastatic castration-resistant prostate cancer remains untreatable and fatal. The new treatment, known as Lu-PSMA-617, takes a new approach, targeting a molecule called PSMA, which is known to be increased on the surfaces of the tumor cells, destroying them and their surrounding microenvironment.
Johann de Bono, MD, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, and Ken Herrmann, MD, Director of the Clinic for Nuclear Medicine at University Hospital Essen, Germany, and an international team of researchers set out to see whether Lu-PSMA-617 was more effective than standard care and recruited 831 patients with metastatic castration-resistant prostate cancer between June 2018 and October 2019. Patients were randomly assigned to receive the treatment plus standard care or standard care alone.
They report that the treatment significantly improved survival of patients by an average of four months, compared with standard treatment. Median survival time was 15.3 for the treatment group and 11.3 months for those receiving standard care. Progression-free survival, or the time before a patient's tumor became worse, was also longer with the treatment: a median of 8.7 months compared with 3.4 months for those with standard care.
The trial also compared side effects, finding that health-related quality of life was not negatively affected, and the team concludes that it is an effective and safe medicine that can improve standard of care for patients with this advanced prostate cancer.
"This is a completely new therapeutic concept; a precision medicine that delivers radiation directly to a high incidence tumor," noted Herrmann. "The treatment was well-tolerated by patients and they had an average of 4 months longer survival with good quality of life. Lu-PSMA-617 can improve the lives of many men with advanced prostate cancer and their families."
de Bono stated: "Our findings show that this potent radioactive medicine can deliver radiation precisely to cancer cells and destroy them, extending patients' lives. I hope men whose tumors have high levels of PSMA can soon benefit from this highly innovative treatment. Currently, the treatment is being appraised by the National Institute for Health and Care Excellence (NICE) for use in the NHS in England and Wales."
"Using the PSMA molecule to directly target prostate cancer cells is the beginning of a new era of precision medicine in urology diagnostics as well as therapy," stated Peter Albers, MD, Head of the Department of Urology, Dusseldorf University, and Chair of the Scientific Office of the EAU. "LU-PSMA-617 was tested in so-called end-stage disease and still showed superiority and this paves the way for studies to treat patients in earlier stages. We have seen similar success in the diagnostic setting, using this molecule to improve the way we stage tumors. This targeted approach will revolutionize the way we approach the treatment of men with prostate cancer in the future."