Genetic mutations in certain genes (oncogenes and tumour suppressor genes) are major drivers in the development and progression of cancer. More than 30% of tumours contain mutations in genes that result in the activation of the PI 3-kinase pathway in cells. This allows these cells to grow uncontrollably and form tumours. Many groups around the world, including our own, are involved in finding drugs to block this particular pathway. A drug (PWT33597) recently developed by us, that was initially funded by an HRC grant, is now in a phase-I clinical trial in the USA. The current project will use the experience we gained in this process to develop more targeted PI 3-kinase inhibitors that do not affect other family members, and thus have minimal side effects. We believe that a ""second-generation"" targeted PI 3-kinase inhibitor will provide a more effective treatment for cancer.