Elucidating the Role of the Thromboxane receptor in prostate cancer

Irish Cancer Society and Health Research Board co-funded research advance their studies into new links to the development and possible treatment of prostate cancer.

On average, 1 man in 7 will get prostate cancer in his lifetime.  Following diagnosis, the majority of prostate cancers respond well to any initial treatment.  However, some can relapse and progress to more serious forms even spreading to other organs.  Most initial treatments for prostate cancer involve regulating the man’s levels of the male hormone testosterone either through therapy, surgery, radiotherapy or, in certain cases, simply through disease monitoring.   In essence, the forms of prostate cancer that go on to relapse have effectively resisted the initial treatment, meaning that alternative treatment approaches are now necessary combined with the fact that the options available to the physician are much more limited.   Hence, understanding why and how certain prostate cancers respond effectively to the initial treatment while others reoccur and progress to potentially more serious, difficult to treat forms is a key scientific question that must be answered if we are to effectively treat and cure such reoccurring, potentially life threatening forms of prostate cancer. 

In a recent study published in 2016 (Mulvaney et al., Oncotarget 7, 73171-73187), headed up by Prof. B. Therese Kinsella, UCD and key national and international collaborators, it was discovered that the levels of a particular protein the Kinsella group has been researching for a number of years in the heart disease area is also significantly increased in prostate cancer.  In scientific terms, the protein in question is called the thromboxane receptor and is, as mentioned, more typically associated with heart disease, being a key target of aspirin widely used to reduce the risk of heart disease.  In their more recent studies published in an April 2017 edition of Biochim Biophys Acta (Molecular Basis of Disease), the Kinsella group sought to understand how such changes in thromboxane receptor expression would impact on the process of how prostate cancer might occur and, in particular, on how it might impact on how prostate cancer reoccurs or relapses in situations of low or reduced testosterone, such as following on from the initial treatment.  Through this recent research, the group have discovered that the thromboxane receptor can not only act as a key promoter of prostate cancer, but can also both mimic but enhance the actions of the male hormone testosterone, including in situations where testosterone levels are reduced or diminished.  Overall, the findings of the research show that the thromboxane receptor greatly contributes to the process of prostate cancer development and provides a mechanism to explain, at least in part, how certain forms of prostate cancer might reoccur and progress even in the absence of testosterone.   By mimicking or enhancing the actions of testosterone, the research suggests that the thromboxane receptor may drive the cancer to reoccur and/or progress including in situations where testosterone levels are reduced or even diminished.  Furthermore, the research suggests that inhibiting the actions of the thromboxane receptor, either alone or in combination with other therapies, may be a novel, alternative approach to prevent or treat prostate cancers, in particular those types that reoccur.  Further research is this area is warranted.

This research, carried out by Aine O’Sullivan, M.Sc. and Eamon Mulvaney, PhD., was funded through a research grant awarded to Prof. Therese Kinsella by the Irish Cancer Society, co-funded by the Health Research Board and the Movember Foundation (Grant No. PCI12KIN (MRCG/2012/3)).  The full research study, accepted for publication on 16^th Jan 2017, can be accessed at Biochim Biophys Acta (Molecular Basis of Disease), volume 1863 (4), pages 838-856.