Gynaecological Cancer Research
DRS IAN & LYNNE HAMSPON
PROJECT TITLE: An investigation into the role of unknown microbial agents in the pathogenesis of cancer
PROJECT TIMESCALE: 1 September 2015 – 31 August 2018
ASSOCIATED PROFESSOR: Prof. K Muir
Most people will know that cancers can arise as a result of environmental and lifestyle factors, for example smoking and the link with lung cancer. What is less well known is that infectious agents have also been shown to have a key role in the genesis and progression of several cancer types. To date we know that these include cervical cancer (Human Papilloma Viruses), liver cancer (Hepatitis B Virus and Hepatitis C Virus) and stomach cancer (helicobacter pylori bacteria).
The Viral Oncology group here at Manchester University believe that the role of infectious agents in cancer development is likely to be much more widespread. But how do we start to look at which agents might be responsible and which cancers do we look at first?
This is not a simple task given that in total there are around 1,400 known species of human pathogens (including viruses, bacteria and fungi) and that within each species there may be many different subtypes. In fact it has been suggested that there are likely to be at least 320,000 viruses alone capable of infecting mammals (the majority of these still awaiting discovery). Trying to select the most likely culprits from this huge number is a seemingly impossible task, made more difficult if the pathogen itself is still unknown. In other words how can you look for something if its existence hasn’t yet been reported in the literature?
In order to scientifically address this problem we needed to come up with a new method of identifying infectious agents that would capture both known and unknown organisms. To do this we honed in on the body’s own first line defence against foreign invaders – the immune system. In particular the protective antibodies to invading pathogenswhich it creates. With clever molecular biology and state of the art computational science we have devised a new procedure that can use the serum of a patient with disease and compare it to that of a disease free individual. The individual serum samples are combined to make a disease sera pool and a ‘normal’ sera pool.
Common anti-bodies are depleted and what is left in the disease pool is genetically analysed. This information is then subjected to intensive computational evaluation using software programs written in house. Simply put, the antibodies present in the disease pool and not the normal pool help signpost us to the infectious agents themselves, and armed with this knowledge we can begin to examine which, if any, might be involved with the cancer.
The first cancer our team opted to look at is that of the ovary, and the Humane Research Trust are currently funding this study. Every year world wide nearly a quarter of a million women will be diagnosed with ovarian cancer and around 140,000 women will die of the disease annually. In the UK it is the 6th most common cancer and unlike some other cancers both the developed and developing nations are affected by it in a similar way. Often called the ‘silent killer’ it tends not to be detected until it has progressed to an advanced stage. This is because it is frequently symptomless and even when symptoms are present they may be mistaken for a variety of other non-life threatening illnesses, such as irritable bowel syndrome, gall bladder problems and diverticulitis.
At the time of diagnosis most tumours will have reached the size of an onion and the outlook for these women is poor. Yet 90% of women could survive beyond 5 years if we could detect it when it is only the size of a peppercorn. Hence there is an urgent need for new markers to enable early detection. Our method has the potential to achieve this.
Following proof of concept and validation of the protocol we would also like to start analysing the sera from men with prostate cancer. This is also built in to the award from the HRT. In the UK approximately 47,000 men are diagnosed with prostate cancer each year and this number has been increasing over the past decade. Cancer of the prostate is the second most common cancer in the UK and the most common cancer of men.
What we primarily hope to achieve, with the help of Trust funding, is an increased understanding of the causative factors of ovarian cancer. The newly developed method that we have put together may help shed some light on whether ovarian cancer (like that of the cervix, liver and stomach) has a virus, bacterium or other microbial agent in its origins. Along the way we may also identify candidate biomarkers for the disease, which are sorely needed. There is much to do, but anything we can contribute to the current knowledge base for this awful disease will be valuable. It may be that the future will see many more cancers being prevented with antibiotic treatments or combated through vaccination programs (as is being done for HPV and cervical cancer). It is to this we aspire!
Where we are now? At the time of writing we have successfully screened two separate pools of ovarian cancer and normal sera and have identified numerous antibodies to pathogens and biomarkers that are either more prevalent or uniquely present in the disease pool compared to normal. A third larger pool of patient sera is now being tested to further refine the list of potential candidates. The good news is that several of them already have a documented association with other cancer types, which gives us confidence in the methodology. It all sounds really simple but in reality it is an extremely complex and time-consuming process. However, with lab work currently ongoing to validate the most encouraging ‘hits’ from our bioinformatics analysis, this year promises to be a key point in the project.
The Team, led by Dr Ian Hampson, a Reader at the University of Manchester the Viral Oncology group, is based at St Mary’s Hospital, Manchester and comprises 4 core scientific staff (soon to be 5) and 2 PhD students. Dr Lynne Hampson (Reader) is the Academic Lead for the ovarian project and works closely with post –doctoral research staff Dr Xiaotong He (Trust funded), Dr Thomas Walker and Dr Anthony Oliver.