Associate professor Kent Søe Department of Clinical Cell biology, Vejle Hospital
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OPEN undersøgelse/kliniske data
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Can diagnosis, monitoring and treatment of bone disease in breast cancer patients be improved? A combined effort using biomarkers, genetic information and translational research - "BoneBio"
It is well known that breast cancer-induced bone disease often continues to progress although patients are given anti-resorptive treatment. Up to 50% of breast cancer patients receiving monthly zoledronic acid treatment have new skeletal related events within 1 year of starting treatment and up to 65% within 2 years. Very similar effects are observed during treatment with the novel drug, denosumab. This clearly suggests that the suppression of bone resorption is far less potent than what could theoretically be expected.
The reasons for this incomplete suppression are without a doubt multi-factorial, but one of the reasons may be that although patients are treated as if they are alike they are most certainly not. With our protocol we would like to put our focus on this issue with a clinical and an experimental approach. In the clinical approach we will address the resorptive behavior of osteoclasts in response to cancer disease and treatment in each individual as detected by the levels of bone biomarkers. In the experimental approach we will test the sensitivity of osteoclasts (generated from different individuals) to zoledronic and see if variations amongst the participants explain this variance in sensitivity.
Hypotheses of direct patient-related relevance
The use of bone biomarkers, CTX and PINP, can predict if patients respond to the anti-resorptive treatment earlier than the present routine methods.
The use of bone biomarkers, CTX and PINP, can predict if patients' cancer-induced bone disease progress earlier than the present routine methods.
SNPs and/or epigenetic differences can explain the variance in sensitivity to zoledronic acid amongst patients.
\nHypotheses relating to in vitro performed osteoclast resorption assays \n \n \n
Osteoclasts from different individuals will display a different sensitivity to zoledronic acid in vitro.
The acidic environment and cytokines generated by growing tumor cells in the bone marrow will directly influence the sensitivity to anti-resorptive treatment and the resorptive behavior of osteoclast in vitro.
SNPs and/or epigenetic differences can explain the variance in sensitivity to zoledronic acid observed in vitro.