Breaking down the barriers
Dr Nikola Bowden uses next-generation genetic profiling techniques to unlock the mysteries of melanoma.
As a molecular biologist, Dr Nikola Bowden appreciates the importance of scientific process, but as a researcher she has also learnt the value of trusting her instincts. It was a gut feeling that prompted Bowden to pursue a line of research that has consequently shifted the central dogma around the role of DNA repair in melanoma development and provided a possible explanation for why the disease is largely resistant to chemotherapy.
Bowden's breakthrough paper on nucleotide expression repair in melanoma, published in the journal Cancer Research in 2010, was the first to report on the relationship between DNA repair pathways and chemotherapy resistance in melanoma.
"Chemotherapy usually works by attacking the DNA of a cancer cell and damaging it so badly that it dies," Bowden explains. "Normally, the DNA repair pathway in a cell will either fix damage, as it does when we get sunburnt, or 'tell' a cell to die when the damage is extreme. But in melanoma this pathway is dysfunctional, so chemotherapy has little or no effect and the cancerous cells continue to accumulate damage and grow."
Because the same DNA repair pathway fixes damage to cells from sunlight, Bowden is now pursuing a hypothesis that dysfunction in the pathway could increase susceptibility to melanoma. Her research project is supported by the Cure Cancer Australia Foundation and the Hunter Medical Research Institute (HMRI).
"I was surprised to find that no one had pursued this line of research before – it is almost as if it had been dismissed because it was too obvious," Bowden remarks.
The researcher's interest in the DNA repair process was sparked by studies she conducted into the rare childhood skin cancer xeroderma pigmentosum (XP), first as a biomedical science Honours student at the University of Newcastle then later as a postdoctoral research fellow.
"XP sufferers have an inherited mutation in their DNA repair pathway and can develop melanomas from very little exposure to sunlight. There are 12 genes that can carry this mutation and I always suspected that those genes may be involved in adult melanoma as well. So now we are looking at those genes in adults and testing their response to UV light exposure."
Bowden has developed some high-powered international collaborations and counts among her mentors Dr Javed Khan, a leading figure from the US National Cancer Institute. She spent six months at the Institute in 2010, at Khan's invitation, where she learnt 'next-generation' DNA sequencing techniques, which allow her to study the entire human genome at once. She has established an important working relationship with pathologists at the John Hunter Hospital and has contributed her skills in whole genome analysis to collaborations with colleagues investigating a range of diseases including leukaemia, schizophrenia, breast cancer, asthma and multiple sclerosis.
Bowden aims to develop diagnostic tests that will identify people at high risk of melanoma and also assist doctors in predicting how a diagnosed cancer is likely to respond to different drug therapies, so they can tailor patient treatment accordingly. She is already witnessing the benefits of this style of personalised medicine. In one puzzling cancer case, on which she was asked to consult, she was able to determine from DNA testing that a patient had two distinct primary tumours, rather than a primary and a secondary. The finding had important implications for the way the cancer was treated.
"Research can be a long road so it is very encouraging to see that sort of immediate benefit in your work," Bowden says. "I would like to think the genetic analysis we are developing in melanoma will be regularly used in practice within the next five years, so we can give patients a better idea from the outset of the treatment likely to help them most."
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