The impact of mutations in PI3K/AKT pathway gene loci on response to PI3K inhibitors

Despite advances in the treatment of breast cancer, the National Cancer Registry of Ireland reported in 2014 that it accounted for 30% of all diagnosed female cancers and 16% of all female cancer deaths. The application of modern technologies to the study of breast cancer has demonstrated that a group of cancer pathways acquire changes due to alterations or mutations which occur in a patient's DNA, which are targetable by a particular group of drugs called PI3K inhibitors.

These advances have led to a shift in cancer therapy to now use new targeted therapies, and away from chemotherapy, which can be damaging also to normal cells in the body. However, breast cancer patients whose tumours don't bear obvious mutations or alterations in their DNA which are predictive of response to the available targeted therapies, are unfortunately being treated with chemotherapy, which often provides only a relatively small benefit and can increase the chance of debilitating side effects. To overcome this major problem, in this project we aim to understand the nature and importance of DNA mutations affecting a particular group of genes, called the PI3K/AKT pathway genes, and then determine if PI3K-inhibitors can be used to best treat them.

A key step towards achieving this goal was that we have been granted access to a large biobank of breast cancer patient tumour samples. We will perform state-of-the art 'DNA sequencing' of the PI3K/AKT pathway genes in these samples to identify and characterise how we can use this knowledge to best predict those patients most likely to respond to the PI3K-inhibitors.

The goal of our project is to identify and understand the importance of PI3K/AKT pathway mutations and the role they play in predicting response to PI3K-inhibitors, resulting in the improved reponse of women who will recieve these therapies.

Award Date
16 May 2019
Award Value
€799,944.09
Principal Investigator
Dr Alex Eustace
Host Institution
Dublin City University
Scheme
Emerging Investigator Awards Full