Bone Therapeutics

Our research is focused on the interactions that occur between bone cells, immune cells and tumour cells, with the goal of identifying new molecular targets, drugs and therapeutic strategies for the treatment of bone diseases, particularly bone metastases from breast and prostate cancer. We are also part of the Bone Oncology Program and have strong collaborative links with members of the Immunology Division and Cancer Division. Our work is currently funded by project grants from Cancer Council NSW and NH&MRC, and a revolutionary team award (program grant) from Prostate Cancer Foundation Australia/Movember.

Previous studies from the Rogers lab identified the molecular mechanisms of action of bisphosphonate drugs, a "blockbuster" class of agents used to inhibit bone destruction in patients with bone metastases as well as in other common bone diseases such as post-menopausal osteoporosis. We showed that these drugs inhibit FPP synthase, an enzyme of the cholesterol biosynthetic pathway, in bone-destroying osteoclasts. Blocking this enzyme prevents the lipid modification (prenylation) of essential small GTPase signalling proteins in osteoclasts.

Inhibition of FPP synthase in circulating monocytes also leads to activation of gamma,delta-T cells and is the cause of the acute phase reaction to bisphosphonate therapy. Our current research includes studies to identify the mechanisms underlying the "pleiotropic" (off-target) effects of bisphosphonates,  including anti-tumour activity that has been observed in preclinical models and in clinical trials of patients with breast cancer and multiple myeloma. Our very recent findings, using state-of-the-art intravital imaging approaches, indicate that these drugs have anti-cancer activity by affecting cells of the immune system (tumour-associated macrophages). We are also applying our  expertise in studying the actions of bisphosphonate drugs in order to gain insights into the pathology of mevalonate kinase deficiency, a rare autoinflammatory disease caused by mutations in an enzyme of the cholesterol biosynthesis pathway.

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