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Towards understanding non-canonical phosphatidylinositol kinases in the maintenance of prostate metabolism.

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Understanding prostate biology key to tackling cancer

Uncovering the role of a specific enzyme in prostate cancer progression could prove critical in the development of new targeted therapeutic drugs.

Health

The prostate, a gland located below the bladder and which plays an important role in male reproductive anatomy, is especially prone to cancer. It is estimated that at least one in seven men in Europe will develop prostate cancer at some stage of their life. Age has been identified as the strongest risk factor when it comes to prostate cancer – men under 50 have a very low risk. However, those reaching the age of 80 or older will have an 80 % risk of developing the disease. “One of the things that makes the prostate different is that it is a really specialised organ,” explains PCAPIP project coordinator Joanna Triscott, postdoctoral associate at the University of Bern’s Department for BioMedical Research, Switzerland. “It is also heavily hormone-dependent.” Scientists believe that this unique biology is one of the things that makes the gland susceptible. More specifically, a strong dependence on hormones called androgens appears to drive changes in the metabolism of cells. A better understanding of how this happens could help researchers to develop more targeted therapies, potentially saving thousands of lives a year.

Role of specific enzymes

The PCAPIP project was launched with the aim of examining this link between cell metabolism and the development of cancer. This research was undertaken with the support of the Marie Skłodowska-Curie Actions programme. “In order to better understand the metabolic process that goes on in prostate cells, I focused on a very specific enzyme,” says Triscott. “Specifically, a family of enzymes called kinases that generate particular lipids, or phosphoinositides.” This Type II phosphoinositide kinase, which relatively few groups have studied in depth before, belongs to a family of enzymes that have been shown to play an important role in other cancer types. “I wanted to develop a fundamental understanding of these enzymes, and then see what they are doing in prostate biology,” adds Triscott. This was achieved by examining the Type II kinases in both mouse models and patient tissue samples. “My hypothesis was that these enzymes are critical regulators of pathways that could be conduits for metabolic change,” she explains.

New cancer therapies

While this research is still ongoing, Triscott and her colleagues have nonetheless made some important discoveries. For example, inhibiting the target enzyme could have an influence on stress compensation mechanisms in the cell. “This is just postulation at the moment, but we think that there could be a relationship here,” she says. “What this means is that if you were to target the Type II kinases with a therapeutic drug, you might be able to deregulate mechanisms that are essential for the survival of progressing cancer cells.” In other words, these enzymes could provide a critical target, and help to make hormone-based therapies more targeted and effective. “Although this is essentially fundamental research, we started out with a translational mindset from the beginning,” notes Triscott. She notes that commercial operations are beginning to look at Type II kinase inhibitors as a potentially marketable cancer therapeutic. She sees the PCAPIP project as part of a larger critical field of work that is laying the foundations to make this possible. “The logical next step I think would be to take these results, and assess their implications for treating prostate cancer and potentially other diseases,” she adds. “Some of the basic mechanisms we are looking at are also relevant for neurodegenerative diseases and diabetes.”

Keywords

PCAPIP, cancer, prostate, diabetes, neurodegenerative, metabolism, cell, biology, bladder, hormones

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