Exploring new molecular and cellular pathways to better define risk in prostate cancer

This project investigated how three sets of DNA mutations - each of which has been linked to prostate cancer individually - work together to make prostate cancer cells multiply and spread, and how they affect cancer stem cells.

These mutations affect mechanisms for sending signals within the cell, known as the Wnt, PI3K and Ras pathways. Problems with these signalling pathways underpin many different cancer types. Each pathway has been independently linked to prostate cancer, but little is known about the interaction between these.

The team have shown in mice that a combination of mutations in genes associated with the Wnt, PI3K and Ras pathways results in more aggressive prostate cancer. In some cases, the combination of mutations to genes in these pathways also resulted in the spread of prostate cancer to other sites such as lymph glands, similar to that seen in aggressive human prostate cancer, and also resulted in shorter overall survival.

They discovered that as the number of mutations in these pathways increased, so did the number of cancer stem cells, suggesting that these pathways could play an important role in cancer development.

Focussing specifically on the PI3K pathway, the Cardiff team analysed human tissue samples to identify the most common genetic mutations in this pathway in prostate cancer cells. Through this investigation they identified a number of mutations that exist within many patients. These mutations could be a potential target for new therapies, and may form the focus of future research.

Grant information

Reference - PG12-16
Researcher - Dr Matt Smalley and Prof Alan Clarke
Institution - Cardiff University
Award - £244,086