Anti-androgen therapy can fuel spread of bone tumors in advanced
prostate cancer
Miniature 3D bone-like tissue models show effects of anti-androgens

Date:
July 7, 2021
Source:
Queensland University of Technology
Summary:
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 has found that anti-androgen treatment can
actually facilitate prostate cancer cells to adapt and grow in
the bone tumor microenvironment model developed by biomedical
scientists.



FULL STORY ==========================================================================
Dr 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
tumour 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 tumours. 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 tumour to assess
the effects of two clinically routinely used anti-androgen therapies -- enzalutamide and bicalutamide -- on the tumour cells.



==========================================================================
"We found that the interactions between the cancer cells, the bone and
the anti-androgens significantly impacted the progress of cancer in the mineralised microenvironment of bone tumours," 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 tumour 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 future, Dr Bock will use her model with patient-derived cells
from patients undergoing prostatectomy, so that it could be used as a personalised preclinical diagnostic and drug testing tool.



==========================================================================
"By screening existing and novel drugs using the bone tumour 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 carry 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.

Prostate Cancer Foundation of Australia CEO Professor Jeff Dunn AO 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.

"Notably, Australia has one of the highest incidence rates of prostate
cancer internationally, with 1 in every 6 Australian men likely to be
diagnosed during their lifetime and around 17,000 men diagnosed each year.

"While survival rates for prostate cancer are high, with over 95% of men
likely to survive at least five years, we must keep up the pace of work
to find curative treatments, especially for advanced disease in the bone.

"There can be no doubt that this research will build on previous
discoveries to help us save lives by stopping cancer from spreading
and claiming the lives of more than 3,000 men a year, as is currently
the case.

"We commend the research team and congratulate PCFA grant recipient Dr
Nathalie Bock for her research achievements.

"This is Australian research excellence at its finest," he said.

========================================================================== Story Source: Materials provided by
Queensland_University_of_Technology. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Zachariah P. Schuurs, Edward Hammond, Stefano Elli, Timothy R. Rudd,
Courtney J. Mycroft-West, Marcelo A. Lima, Mark A. Skidmore,
Richard Karlsson, Yen-Hsi Chen, Ieva Bagdonaite, Zhang Yang,
Yassir A. Ahmed, Derek J. Richard, Jeremy Turnbull, Vito Ferro,
Deirdre R. Coombe, Neha S.

Gandhi. Evidence of a putative glycosaminoglycan binding
site on the glycosylated SARS-CoV-2 spike protein N-terminal
domain. Computational and Structural Biotechnology Journal, 2021;
19: 2806 DOI: 10.1016/ j.csbj.2021.05.002 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210707112445.htm

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