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Division of Cancer and Stem Cells

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Siwei Zhang

PhD student (Cancer & Stem Cells), Faculty of Medicine & Health Sciences

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Research Summary

In the UK, ovarian cancer is the fifth most common cancer in females and the most common cause of gynaecological cancer death (cancer research UK). Their association with high morbidity and mortality… read more

Current Research

In the UK, ovarian cancer is the fifth most common cancer in females and the most common cause of gynaecological cancer death (cancer research UK). Their association with high morbidity and mortality is due to the fact that around 75% of patients have progressed into advanced stage (presence of metastatic spread beyond the ovaries, FIGO(the International Federation of Gynecology and Obstetrics) stages III or IV) when they are diagnosed with ovarian cancer (Dinh et al., 2008).

The integration of surgical cytoreduction and platinum-based (platinum and platinum-taxane) chemotherapy has been the cornerstone of ovarian cancer treatment (Kwa & Muggia, 2014). The current standard regimen for ovarian cancer is almost universally carboplatin and paclitaxel which can achieve similar curative effect as cisplatin and paclitaxel but is less toxic (Ozols RF., 2006). Although most women with advanced ovarian cancer initially respond to platinum-based first-line therapy, a large number subsequent relapse and further cancer progression occurs. The 10 year survival rate is 35%. It is, therefore, important to find prognostic factors and novel treatments.

Calpain is a cytoplasmic cysteine protease requiring Ca2+-regulated activation. It is involved in several of cellular processes such as signal transduction, cell proliferation, cell cycle progression, differentiation, apoptosis, membrane fusion, and platelet activation. Deregulation of its activity has been involved in various pathological conditions such as neurological disorder, cancer, cataract and diabetes etc. A previous IHC study conducted by our group (Storr S.J. et al., 2012) showed that high expression of calpain-2 significantly associated with resistance to platinum-based adjuvant chemotherapy, poor progression-free and overall survival. And the association between calpain-2 expression and overall survival is independent from platinum sensitivity. So calpain-2 does not wholly depend on the platinum sensitivity to have an impact on survival.

The above findings led to our interest in the role of calpain system in ovarian cancer treatment response, especially the response to chemotherapy. We plan to verify initial IHC data using a larger patient cohort, that will allow a more detailed analysis of the different ovarian cancer subtypes, and to conduct a range of in vitro experiments using established ovarian cancer cell lines, of varying platinum sensitivity, to understand the mechanisms whereby calpain is affecting treatment response. This project has the potential to identify members of the calpain system as prognostic factors and that may be useful clinical targets for ovarian cancer.

School of Medicine

University of Nottingham
Medical School
Nottingham, NG7 2UH

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