Lay summaries written by our students of published research papers
Paper: N. A. Bonito, J. Borley, C. Wilhelm-Benartzi, S. Ghaem-Maghami, and R. Brown, “Epigenetic regulation of the homeobox gene MSX1 associates with platinum resistant disease in high grade serous epithelial ovarian cancer.,” Clin. Cancer Res., Jan. 2016.
Ovarian cancer is the fifth most commonly diagnosed female cancers in the UK and high-grade serous ovarian cancer (HGSOC) is one of the most diagnosed forms of epithelial ovarian cancer. While the majority of HGSOC patients respond to platinum-based chemotherapy well, a small group of patients will not respond and subsequently have very poor survival. It is important to identify which patients will respond to treatment and which will not before treatment begins, as this reduces delay in treating patients with the right treatment and reduces unnecessary discomfort for the patients. One way of dividing patients is by using “biomarkers”. Biomarkers are molecules found in the body that are different in people who develop a certain disease or condition to people who don’t. They can be detected in blood, bodily fluids or tissues. One of the ways biomarkers are useful in cancer research is they separate people who will or will not respond to treatment.
Your DNA is what makes you individual and unique and like a library it contains all the information from your parents and thousands of generations before them. Your library contains hundreds of books called genes. These “genes” can be read individually or together to create an idea and this new idea is your genes being “expressed”. But this library needs to be controlled somehow. Your epigenome is the librarian in your library. The librarian manages what books you take out, how many you can take out and how long you can take them out for. By coordinating how the books (or genes) are accessed, the librarian can regulate what is happening in each part of your library and have it working in perfect order. Bonito and colleagues have been investigating how loss of control of a gene called MSX1 (which can cause cancer cell death) by the epigenetic librarian can allow tumours to be resistant to chemotherapy, thus compromising survival. Conversely, patients who have not lost control of this gene are more likely to be sensitive to chemotherapy and have better survival. By identifying patients who won’t respond to chemotherapy early, doctors can potentially reduce the number of patients who relapse and improve the diagnosis of these patients, hopefully giving them longer to live.
Caitriona Tyndall, CRUK Centre PhD Student
Paper: A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, J. R. Marchesi, B. Lehne, R. Bhatia, D. Lyons, E. Paraskevaidis, J. V Li, E. Holmes, J. K. Nicholson, P. R. Bennett, and M. Kyrgiou, “Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity.,” Sci. Rep., vol. 5, p. 16865, Jan. 2015.
Cervical cancer is the 12th most common female cancer diagnosed in the UK, with approximately 3,000 new cases each year. The precursor for cervical cancer is a disease called cervical intraepithelial neoplasia (CIN). This disease is commonly caused by HPV (Human Papillomavirus) infection. HPV is frequently present in women, but only a small percentage of these women develop CIN and smaller number still develop cervical cancer. The reasons behind this are largely unknown. CIN is detected through cervical screening tests (commonly known as smear/PAP tests), which are available from the age of 25 – 60. It is important for a woman to undergo regular smear test throughout her lifetime, especially if CIN is detected. This allows females with CIN to be monitored and treated in the hopes of preventing cervical cancer. However, not all women develop CIN and not all CIN patients develop cancer.
It is important to understand what separates the women who do develop cancer with the ones who do not. One way of differentiating these patients is by understanding the vaginal microbiome. The vaginal microbiome is the entire compliment of bacteria in your vagina. These bacteria protect and maintain a healthy vaginal environment. When the microbiome is compromised, this can lead to infections such as candidiasis (known as thrush) or HPV. Mitra and colleagues have shown that patients with different levels of CIN and cervical cancer have different microbiomes. For example as disease progresses from CIN to cancer, the levels of Lactobacillus spp. decrease, while other bacterial species increase. Lactobacillus is an important bacterial species in maintaining a healthy vaginal environment and protecting from viral infection. This is important work in adding to our understanding of why only a small percentage of women with CIN develop cervical cancer. It is thought that by monitoring the vaginal microbiome as well as CIN progression, doctors could potentially be able to identify the patients who will develop more severe stages of CIN and subsequently cervical cancer. By identifying these patients early there is the potential to reduce cervical cancer cases in the future.
Caitriona Tyndall, CRUK Centre PhD Student