Importance of attenuating CXC-chemokine promoted angiogenesis as the mechanistic basis to enhanced Taxotere response in androgen-independent prostate cancer

Dr David Waugh & Dr Joe O'Sullivan, Queen's University, Belfast

Taxotere is a drug that has recently been approved for use in the treatment of metastatic androgen-independent prostate cancer (AIPC) in both the US and UK. This drug is given to patients in conjunction with a glucocorticoid agent known as dexamethasone. The combination of Taxotere and dexamethasone improves not only a patient’s quality of life and pain control but also confers a modest survival benefit to AIPC patients. This combination therapy is now the standard of care for metastatic AIPC and is the first chemotherapy regimen to confer a survival advantage in this group of patients. However, it remains to be established why this combination works in treating AIPC patients. Preliminary observations from experiments conducted in our laboratory have shown that the combination of dexamethasone enhances the ability of Taxotere to suppress new blood vessel growth and development. The generation of new blood vessels, a process known as angiogenesis, is essential in order to permit prostate cancer cells to access a continuous supply of nutrients and oxygen that enables the tumour cells to grow uncontrollably. Therefore, the work that we propose to conduct with funding from the Prostate Cancer Research Foundation will further investigate our proposal that the success of this chemotherapy regimen in AIPC is associated with its increased ability to suppress angiogenesis. We will continue to conduct studies on our established laboratory models of prostate cancer to test this hypothesis. Furthermore, we will initiate prospective studies on AIPC patients receiving these agents to determine whether their response to these agents correlates with a suppression of pro-angiogenic protein levels detected in their blood. If we can demonstrate the association of Taxotere/dexamethasone therapy with reducing angiogenesis, then our observations may encourage the testing of further, more potent anti-angiogenic agents in combination with Taxotere in clinical trials of AIPC. Ultimately, we propose that this research project in tandem with similar investigations will have the promise of providing an increased prognosis for patients with AIPC.  

Project commenced
March 2007

Length of project
1 year

Amount Supported
£23,000