Researcher Ilirjana Bajrami was recently awarded the Sir Antony Driver Prize for outstanding contribution to breast cancer research and here shares her experience of working in the field.
Where it all begins
Breast cancer has been the focus of my scientific research for many years. As a young student, I was fascinated by our DNA, the ‘instruction manual’ that controls the cells in our bodies.
My interest in DNA began at university whilst studying for a biochemistry degree, and led to me working for a small pharmaceutical company called Antisoma for a year as part of my degree. My research there involved looking at the ways in which normal DNA inside healthy cells can develop faults which turn them into cancer cells.
During my time at Antisoma, I learnt about the various ways in which we can fight cancer cells by finding their 'weak spots', which tend to be linked to the ways cancer cells adapt to survive.
One such adaptation is creating their own blood vessels that supply them with extra nutrients for their excessive growth. A way to stop this is to block the new blood vessels from forming, which should limit the growth and spread of the cancer.
Vadimezan, the drug I worked on during my placement year, has recently been tested in patients for lung, prostate and a specific form of secondary breast cancer (called HER2 negative), and the drug has demonstrated good potential as a treatment for some patients.
Joining the Breast Cancer Research Centre
After university, my greatest passion was to discover new findings about the complexity of cancer and to ultimately contribute to developments in treatments. In 2007, I joined the Gene Function lab at the Toby Robins Breast Cancer Research Centre working as a scientific officer under the supervision of Professor Alan Ashworth and Dr Chris Lord.
The ongoing research in this lab is groundbreaking, providing new insights into the development of pioneering treatments for breast cancer that are tailored to each patient and their specific cancer.
The lab team has a rich history of making groundbreaking discoveries, including Professor Ashworth’s team discovering the second breast cancer susceptibility gene, BRCA2. This gene, when faulty, is responsible for 5-10 per cent of breast cancers.
Results of tests for an inherited fault in BRCA2 can be used to measure the risk of developing certain types of cancer, including breast but also ovarian and prostate cancers.
This discovery has had a substantial impact because those carrying this hereditary fault now have the option of undertaking preventative strategies, such as preventative surgery, so that they never develop those cancers. Professor Ashworth and his colleagues at the Centre also set about understanding how the BRCA2 gene actually works.
This led them to identify a class of drugs that can specifically target cancer cells with faulty BRCA2. These drugs are known as PARP inhibitors. You can read more about how they work in this blog.
To cut a long story short, faulty BRCA turned out to be the Achilles heel of cancer cells carrying those faults, and it could be severed with PARP inhibitors. And since then this type of drug has shown very encouraging results in patients with BRCA faults.
The success of this research encouraged me to investigate how we could apply this sort of approach to the development of new treatments – what other weaknesses did the cancer cells have that I could exploit?
My initial focus was to identify new combinations of drugs to treat triple negative breast cancer (TNBC). This type of breast cancer is aggressive, typically affects younger women and currently has limited treatment options. I studied the impact of a combination of a PARP inhibitor and another type of drug on TNBC growth.
The results showed that by using both FK866, the catchy name for the second drug, as well as a PARP inhibitor blocked the growth of TNBC tumours. The drug FK866 works by inhibiting the molecule NAMPT.
These findings suggest that further investigation of the combination of a PARP inhibitor and an NAMPT inhibitor might be a good strategy for the treatment of TNBC.
I was also able to identify other faulty molecules and genes that, in a similar way to the BRCA, caused cancer cells harbouring these defects to stop growing when treated with a PARP inhibitor.
These other molecules and genes are potential treatment targets and include molecules called miR-107 and miR-222 and the gene CDK12. The CDK12 gene has recently been shown to be faulty in a large number of ovarian and breast cancer patients, suggesting that mistakes in this gene should be investigated as a potential new treatment target in the future.
Although this research has shown encouraging results, we still need more research like this to provide treatment options for even more patients.
Two and a half years ago I decided to embark on a new project, as part of my doctorate degree, focusing on identifying treatments for breast cancer patients with faults in the gene CDH1. Faults in this gene contribute to the development of breast tumours, including 56 per cent of lobular breast cancers (a particular type of the disease).
I am currently searching for the best therapies to treat patients with this particular fault in their DNA. I am hoping that in the near future we will reach a point at which personalised medicine, where treatment is tailored to the patient’s tumour, becomes a reality.
Achieving this goal will drastically improve patients’ response to treatments and reduce unwanted side effects that are associated with conventional, less specific, treatments such as chemotherapy. It’s so exciting to be part of this important area of research.
Myself and everyone at the Research Centre are extremely grateful to Lord Driver and his family for helping to establish the Centre but also for their continued support of our work. In particular I’d like to pass on my thanks for selecting me as the recipient of the Driver Prize this year.
Now back to the lab to continue the pioneering research!