Researcher: Dr Paul Mullan
Location: Queen's University Belfast
Project title: Finding new ways to find and treat aggressive breast cancers with poor responses to current chemotherapy treatments
Key area: Secondary breast cancer
Triple negative breast cancer is a form of the disease which has limited treatment options because it cannot be treated using targeted therapies available for other types of breast cancer. Even in breast cancers that should respond to targeted therapies, some cases are, or become, ‘resistant’ to chemotherapy treatment and a protein called TBX2 appears to be linked to these cases. Dr Mullan’s team hopes to unravel the interactions between TBX2 and another protein called KDM1A, to provide insights into which cancers may not response to chemotherapy and to find new ways to target these cancers.
The science behind the project
When the DNA in normal breast cells gets damaged, the cell will ‘recognise’ that the instructions from DNA in the cell are faulty and it will permanently stop dividing or die. However, in some breast cancers, cells keep dividing in the presence of damaged DNA – even if the DNA has been damaged by chemotherapy.
One of the proteins that helps breast cancer cells to keep growing in this situation is called TBX2. Dr Mullan’s team believes that in some breast cancers, including triple negative breast cancers, TBX2 may work with a protein called KDM1A to help cells grow even after chemotherapy treatment, resulting in worse outcomes for these patients.
Dr Mullan’s team will map out all the interactions that TBX2 and KDM1A have with genes and other molecules to find out how these proteins help breast cancer cells to continue dividing in the presence of DNA damage. The researchers will then confirm the presence of these molecules in several sets of independent breast cancer samples from patients.
This mapping exercise will give Dr Mullan’s team a set of proteins that could be used to indicate which breast cancers may not respond to current chemotherapy drugs. In addition, they aim to identify proteins which could be targeted with new chemotherapy drugs.
What difference will this project make?
This project could provide us with a way to predict in advance which patients may not respond to current chemotherapy treatments, both for triple negative breast cancer and some other breast cancer subtypes. Most importantly, this work may also provide opportunities for the development of new targeted drugs specifically for triple negative breast cancer, a type of the disease which currently has very limited treatment options.