Brystkræftpatienters variable sensitivitet mod antiresorptiv behandling
Each year approximately 4,800 women are diagnosed with breast cancer (BC) in Denmark. Approximately 62,000 women live with this diagnosis, but around 2,500 have metastases to the skeleton, which apart from being incurable also results in reduced quality of life due to strong pain, reduced mobility and increased fracture risk. As part of the standard treatment BC patients are most often treated with zoledronic acid to prevent the bone destructive processes activated by cancer cells. However, within one year 50% of patients have new damages to their bones and after two years it is up to 65%. The target of zoledronic acid is the bone resorbing osteoclast. The reasons for the incomplete suppression of bone resorption in BC patients can be multi-factorial, but one of them may be that patients are not alike and therefore respond differently to the same treatment. In our project we will focus on precisely this issue by investigating the bone resorptive potential of osteoclasts in the presence of various cytokines produced by cancer cells as well as their sensitivity towards zoledronic acid.
Through the use of a cell culture model system we will investigate if the incomplete effects of zoledronic acid can be caused by: 1) variance in sensitivity between individuals, 2) low pH generated by cancer cells which reduces the potency of treatment and 3) cytokines produced by cancer cells which reduces the potency of treatment.
All experiments will be performed with cells obtained from 50 female blood donors and not from cancer patients. This is done due to ethical and health related considerations. Primary human osteoclasts are generated in vitro according to our well-established protocol. This enables us to compare the sensitivity to zoledronic acid across donors and whether reduced pH and cytokines affect this sensitivity. Using this in vitro model system we have previously demonstrated that there are significant differences between the ability of osteoclasts to resorb bone depending on the gender of the donor. We therefore find it valid to also use this approach to reach our present aims.
Results from this particular project can improve our understanding of how the microenvironment generated by cancer cells can affect the success of treatment with e.g. zoledronic acid and how this may be dependent on biological differences between patients. In other words the entire project will highlight the importance of using treatment strategies that are tailored to individual patient more than it is today in order to optimize the treatment of cancer induced bone disease.
1. juli 2016 - 30.juni 2019
Lektor, cand.scient, Ph.d. Kent Søe, Klinisk Cellebiologi, Vejle Sygehus
Professor, PhD, Jean-Marie Delaissé, Klinisk Cellebiologi, Vejle Sygehus
Publikationer og aktiviteter
Se link til Anaïs Marie Julie Møller's publikationer m.v. på SDU.dk - link
Siden er sidst opdateret 11-08-2017.
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