Using genetics to treat ovarian cancer
Medical oncologist and clinical scientist, Professor Charlie Gourley, is improving the outcomes of patients with ovarian cancer by matching them to the right drugs.
Ovarian cancer is one of the most common types of cancer in women. It mainly presents in women over 50 but it can also affect younger women.
Approximately 7,500 new cases are diagnosed in the UK each year and although the incidence rate has been stable since the early 1990s, mortality remains high, with only 35% of patients surviving for 10 or more years.
There is currently no test widely available to check women’s ovarian health. Combined with symptoms that can easily go unnoticed, it is no wonder the disease is habitually known as the silent killer.
In recent years, the discovery that ovarian cancer has a strong genetic component, has been a game changer. Up to 44% of patients who inherit a harmful mutation in the BRCA1 or BRCA2 gene will develop the disease before age 80.
The University’s Professor Charlie Gourley, a medical oncologist specialising in the treatment of ovarian cancer, has been leading research to identify and validate new drug therapies for ovarian cancer.
We ask him about his work, what makes him tick and the outlook for ovarian cancer treatment.
Can you tell us a little bit about your work?
As well as working as an oncologist treating ovarian cancer, I run a genetics lab. There are three aspects to my work: looking after patients with ovarian cancer, doing clinical trials to evaluate new therapies and examining the molecular changes that are driving ovarian cancers.
I keep a foot in the lab and a foot in the clinic, which puts me in a good position to develop new therapeutic strategies and treatments.
There are at least five different types of ovarian cancers, and even within these types there are important molecular differences that will affect the response to treatment. Until about ten years ago all ovarian cancers were treated in the same way, but it has become clear that to improve treatment we need to understand what drives each type of cancer.
One of my team’s priorities is to look at what is driving some of the rarer ovarian cancer types, such as low grade serous ovarian cancer (LGSOC) which tends to affect younger women and does not respond well to chemotherapy, and find new, more effective treatments.
Our latest paper on the first randomized clinical trial in patients with LGSOC shows that a new drug works better than all other treatments, doubling the time before relapse. We are now looking at tumour samples from these patients for clues that could help us understand if some are more likely to benefit from the treatment than others.
How did you become interested in this field of work?
As a medical student at the University of Glasgow, I decided to study for an intercalated degree in genetics. I was inspired by a lecturer who was both a researcher and a medical oncologist. He made a very good case for going into oncology if you are interested in research related to genetics or molecular biology. I’d say that about three quarters of my learning during the genetics degree was relevant to cancer and by the time I finished medicine I’d decided to specialise in oncology.
My first oncology job was in Edinburgh, and on the first day I met Hani Gabra, an ovarian cancer oncologist who ran a research lab and with whom I went on to do my PhD.
I was very lucky, because there was another ovarian cancer oncologist, Professor John Smyth, at Edinburgh, who in 1981, and before anyone else had thought of doing this, had set up a big database of ovarian cancer patient profiles. This became an invaluable resource for my lab as it made it possible for us to link the molecular analyses of patient samples recovered from the pathology archive to their clinical outcomes collected in the database. Thus, we were able to see what molecular changes were associated with better or worse outcomes. We continue to grow and use this database today.
It is all about meeting the right people and being in the right place at the right time!
What do you love the most about what you do?
I love the discovery aspect of research, getting new results in the lab or the clinic that no one else knows about yet, and that could really change things. For example, we were one of only five places in the world where the first clinical trial with the drug Olaparib, which has become a game-changer for patients with ovarian cancer, took place. I remember the first and second patients we gave the drug to and starting to see them get better very quickly. We knew at that time that there was a high chance that this drug could change the management of ovarian cancer.
Over the course of the next 10-12 years, we had a major role in the subsequent trials leading to the approval of Olaparib for the treatment of women with advanced ovarian cancer. Because we were part of these trials in Edinburgh, our patients were able to benefit from this drug years before it was licensed.
That is really why you do it, for new drugs that can really help patients.
What would you say has been the biggest challenge?
On a personal level, balancing everything is quite challenging. It is difficult to find the time to do everything, but that is quite a boring answer!
One frustration is trying to get the NHS in Scotland to grasp the opportunities presented by new genetic sequencing technologies. Using more complex genetic testing in cancer patients could actually save money.
We were doing routine BRCA gene sequencing in ovarian cancer patients before the rest of the UK, but since the 100,000 Genomes Project was funded in England in 2013, it feels like we are playing catch up. We don’t really have an equivalent in Scotland and we don’t want to fall behind.
What impact has COVID-19 had on your work?
It hasn’t had a massive impact to be honest. Patients are still coming through and we are still doing clinical trials. Although the trials were stopped for a couple of months, Edinburgh was one of the first places to restart them.
In terms of the lab, PhD students were the most affected as they have to get things done in a pretty tight timeline. For my research group as a whole, we spent a lot of time during lockdown writing up papers.
What do you plan to do next? What does the future of ovarian cancer therapy look like?
We are trying to understand the mechanisms of resistance to drugs like Olaparib so we can attack those mechanisms and get a bigger beneficial effect.
We also carry out large drug screens to identify new treatments for rare types of ovarian cancer and work out which patients they should be given to in clinical trials. We are working with drug development teams at the Cancer Research UK Edinburgh Centre as well as pharmaceutical companies to target drugs to specific cancer subsets.
I am very hopeful about advances in genome sequencing. We are just pulling together the data from the whole genome sequences of 120 Scottish patients and finding novel cancer features that are likely to impact how we treat patients in the near future.
Ovarian cancer treatments are definitely improving. PARP (Poly (ADP-ribose) Polymerase) inhibitors like Olaparib are having a big impact on patients. We know these drugs delay the time until ovarian cancer comes back; what we hope is that they also cure more patients. These data should be available soon; the signals so far are encouraging.
Charlie Gourley is Professor of Medical Oncology and the Clinical Director of the CRUK Edinburgh Centre, and Director of the Nicola Murray Centre for Ovarian Cancer Research.
The Cancer Research UK Edinburgh Centre brings together cancer scientists and clinicians from across the University of Edinburgh, delivering outstanding cancer research and improved patient care.