Thromboxane (TX)A2 -mediated PRK1 signalling in Prostate Cancer: Does the TXA2 Receptor Serve as a Chemotherapeutic Target?

Key Information

Cancer type: 
Research Institution: 
Grant Amount: 
Start date: 
December 1, 2012
End date: 
December 1, 2016

Scientific Project Abstract

The lifetime risk of developing cancer is around 40%, and rising. Prostate cancer (PCa) is one of the most common cancers among men globally and in Ireland, with relatively poor survival rates. Reducing the risk of disease is a key goal of modern cancer-prevention strategies. It has been suggested that frequent use of the widely used pain-killer and anti-blood clotting agent Aspirin greatly reduces the risk of many common cancers. However, the way in which it does so is currently unknown. One such proposal is that the benefits of Aspirin as an anti-cancer agent may be due to its ability to inhibit the generation of thromboxane, a substance more typically known for its role in blood clotting in the body. In addition to this, increased levels of thromboxane and of its target protein, the thromboxane receptor or, in short, the TP, have recently been strongly implicated in a number of common cancers, including PCa. Hence, it has been suggested that the TP may be a good anti-cancer target for drug development. In fact, in very promising pilot studies, we have developed and tested some new compounds that we specifically designed to block/inhibit the TP and that found our compounds were very effective in inhibiting cancer in the lung in an experimental mouse model of cancer. Furthermore, in other studies within the main applicant (Kinsella)'s group, we have also discovered that the same TP target directly binds and regulates the action of PRK1, another protein which is actually already known to be very important in PCa. Hence, due to the increasing evidence of the importance of thromboxane and its receptor (the TP) in PCa combined with our discovery that the TP binds and regulates PRK1, an already recognized target in PCa, we reason/hypothesize that we may have uncovered 'the key that explains the role of thromboxane in PCa,' and possibly in other cancers. Hence, the over-arching aim of this study is to examine the importance of the interaction of the TP with PRK1 for the role of thromboxane in PCa. Furthermore, using animal models of cancer, we will investigate whether inhibiting the action of thromboxane, by blocking the TP from working, is a useful approach in treating PCa or preventing its spread to other organs, such as to the lung.

For the non-scientist

One-line description: 
Determining if molecules involved in blood clotting may be potential drug targets for prostate cancer
What this project involves: 
It has been suggested that frequent use of pain-killer and anti-blood clotting agents such as aspirin greatly reduces the risk of many common cancers. The reason behind this is currently unknown however it is thought that inhibition of a substance involved in blood-clotting may play a role. This substance, called thromboxane, and its target protein, thromboxane receptor, have been strongly implicated in a number of common cancers, including prostate cancer. This project aims to determine if targeting of the thromboxane receptor represents a potential new drug-target for prostate cancer.