Ovarian Cancer Perspectives: Q&A with Dr Michelle Lockley

March is Ovarian Cancer Awareness Month. Ovarian cancer is the sixth most common cancer in women in the UK, with around 7,400 new cases diagnosed each year. There are approximately 4,200 ovarian cancer deaths in the UK every year, making ovarian cancer the sixth most common cause of cancer mortality in women. At Barts Cancer Institute (BCI), Queen Mary University of London, ovarian cancer is one of our main areas of focus, with an emphasis on translational research.

In recognition of Ovarian Cancer Awareness Month, we spoke with Dr Michelle Lockley, Group Leader and clinical researcher in BCI’s Centre for Cancer Cell and Molecular Biology. Dr Lockley’s research group focuses on improving treatments for women with ovarian cancer, particularly for those whose tumours are resistant to chemotherapy.

What motivated you to focus on ovarian cancer as a clinical researcher?

Ovarian cancer poses a particular challenge in that chemotherapy initially works very well, however with repeated administration its effectiveness decreases and the cancer becomes resistant to the therapy. Therefore acquired chemotherapy resistance is a major problem for ovarian cancer. If we could preserve some of the initial chemotherapy sensitivity for the duration of a patient’s illness, we could extend survival. So finding strategies that could make this happen is of interest to me. Another aspect of ovarian cancer that interests me is the huge variety that exists in this cancer. There are many different types of ovarian cancer, and each tumour type has its own set of challenges to overcome.

It is important to me that the research I do in the laboratory is relevant to the patients I treat and as a clinical researcher it is valuable - and perhaps rare - that I can bring a clinical perspective into my research.

What is your research focus currently?

Chemotherapy resistance is one of the focuses of my ovarian cancer research, and I aim to improve treatment options for resistant ovarian cancer types. One of the strategies we are pursuing for this currently, in collaboration with Professor Trevor Graham, is an evolutionary approach to managing chemotherapy resistance known as Adaptive Therapy. This involves tailoring treatments for individual patients as their cancer evolves in response to the treatment over time. The pre-clinical work for this project, conducted by one of our Cancer Research UK (CRUK)-funded Clinical Fellows, Dr Helen Hockings, has shown promise in the laboratory and indicates that this approach will preserve chemotherapy sensitivity and prolong survival. We have been working with the CRUK Barts Centre Patient and Public Involvement Research Advisory Group to develop a clinical trial so that women can potentially benefit from this strategy in the future.

Another of my clinical research interests is ovarian germ cell tumours. These very rare tumours occur in young patients and have high rates of cure. We have done a lot of clinical work on these, thinking about how we describe their pathology, how we can manage them in terms of their chemotherapy and surgery, and working with international consortia that are devising clinical trials that will recruit across the world for these rare cases. We hope to develop some more translational research ideas for these cancers going forward.

You lead the Barts Gynae Tissue Bank – why is this such an important resource for research?

It is essential that the research we conduct is relevant to patients. Cell lines and animal models are an important tool for cancer research, but we also need to understand what is happening in human cancers by using human samples. So this was the initial motivation for setting up the Barts Gynae Tissue Bank, which collects, stores and shares tissue samples for translational research into gynaecological cancers.

Over the years, and with the support of BCI, the tissue bank has been able to grow and we now collect tissue from multiple London centres, including Barts Health NHS Trust, University College London Hospital and St George’s Hospital. The tissue bank supports the research of internal BCI researchers who may be working on their own or in collaboration with other research centres. Ultimately, the tissue bank allows us to ensure that the research we are doing at BCI reflects the cancers we see in our patients.

What do you anticipate will change in the next 5 years in terms of ovarian cancer treatment?

The big change that we are currently living through is the widespread implementation of PARP inhibitors (drugs that inhibit the repair of damaged DNA in cancer cells, leading to cell death). We are now entering an era where the majority of patients with high-grade epithelial ovarian cancer are likely to receive a PARP inhibitor at some point during their treatment. We know that PARP inhibitors extend progression-free survival, and we are excited that there may be subgroups of patients that we could potentially cure with these treatments; however, we have to wait for data from clinical trials to determine this.

There are also some unanswered questions about how we can use these PARP inhibitors - can we use them repeatedly, can we use them in combination with other treatments? So, I think looking at how we can use PARP inhibitors better may be a focus over the next 5 years.

The other big question is why immune checkpoint inhibitors (drugs that reinvigorate the body’s immune system to recognise and kill cancer cells), which have shown success in a variety of cancer types, do not work for the treatment of the most common types of ovarian cancer. So perhaps understanding why these immune checkpoint inhibitors are unsuccessful and looking at other ways of manipulating the immune system to target ovarian cancer will be an important strand of research over the next 5 years.