Anti-androgen therapy can fuel spread of bone tumors in advanced prostate cancer

1200px-Prostate_adenocarcinoma_2_high_mag_hps (1) Nephron- CC BY-SA 3.0
High magnification micrograph of prostate adenocarcinoma. Needle core biopsy. HPS stain. Credit: CC BY-SA 3.0 - Nephron

Dr. Nathalie Bock, under the mentorship of Distinguished Professor Dietmar Hutmacher, from QUT Centre for Biomedical Technologies, has focused her research on bone metastases from breast and prostate cancers.

She developed 3D miniature bone-like tissue models in which 3D 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 a limited effect on the microenvironment of prostate cancer bone tumors. The team’s findings are published in Science Advances.

“We wanted to see if the therapy could be a contributor of cancer cells’ adaptive responses that fuelled bone metastasis,” Professor Hutmacher said.

“We developed an all-human, microtissue-engineered model of metastatic tissue using human bone-forming cells, prostate cancer cells and 3D printing.”

Cancer biologist Distinguished Professor Judith Clements 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,” Professor Clements said.

“This means that the efficacy of these therapies is compromised in the presence of the bone microenvironment.”

Professor 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, Dr. 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,” Dr. Bock said.

“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 carries the potential of severe side-effects, and which may not work for them.”

This research was supported by the National Health & Medical Research Council of Australia, Australian Research Council, and the Prostate Cancer Foundation of Australia.


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Materials provided by the Queensland University of Technology. Content may be edited for clarity, style, and length.


 

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