Authors: Hollie Franklin, Future Science Group
Ovarian cancer is currently one of the most difficult cancers to diagnose early because of a lack of symptoms that are unique to this disease. It is also of great concern as it is usually diagnosed at a late stage and so the mortality rate is high, this is due to the absence of warning symptoms.
Scientists at the A*STAR Institute of Medical Biology (IMB) and the Bioinformatics Institute (BII; Singapore) have identified a biomarker of ovarian stem cells, which may lead to the early detection and personalization of treatment for ovarian cancer. Early detection allows for more effective treatment at an early stage of the illness. Their results are published in a recent online issue of Nature Cell Biology.
The biomarker identified, termed Lgr5, is found on a subset of cells of the ovarian surface epithelium. This molecule has previously been successfully located in other tissues but this is the first time it has been successfully located in the ovary. This means that the researchers have also identified an important epithelial cell population in the ovary, one that produces Lgr5, which controls the development of the ovary.
The most prevalent and lethal type of ovarian epithelial cancers is high-grade serous ovarian carcinoma (HG-SOC). Patients with HG-SOC have only a 30% chance of surviving more than 5 years following diagnosis. HG-SOC is not well understood and has a limited number of biomarkers available for clinical use.
BII scientists applied bioinformatics analysis on big cancer genomics data and identified genes that could be used in the personalization of treatment of HG-SOC. The CHEK2 gene has been identified as an effective prognostic marker of patient survival. HG-SOC patients with mutations in this gene usually died within 5 years if diagnosis, possibly because CHEK2 mutations are associated with poor response to currently available treatments.
Following a HG-SOC diagnosis, mortality remains high. This is probably due to the fact that patients are administered similar chemo- and radio-therapy regimens, despite the fact that HG-SOC tumors are highly variable. It is hoped that the finding of the researchers at A*STAR IMB and BII will lead to more personalized and targeted treatment, with treatment tailored to different subgroups of patients.
David Lane, Chief Scientist, A*STAR, explained, “These findings show how the various research institutes at A*STAR offer their expertise in developing new approaches to examine different aspects of the same disease that have not been successfully studied before, such as ovarian cancer. The diverse capabilities and knowledge of our scientists allows us to investigate diseases holistically, from diagnosis to treatment.”
Sources: Ow GS, Ivshina AV, Fuentes G, Kuznetsov VA. Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures. Cell Cycle 13(14), 2262 (2014); Ng A, Tan S, Singh G et al. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat. Cell Biol. 16(8), 745–757 (2014); A*STAR press release