EARLY DETECTION OF OVARIAN CANCER
Ovarian cancer is the ninth most common cancer in Australian women and the sixth most common cause of cancer death. Every year, around 1200 Australian women are diagnosed, and 800 die from this disease. Due to the lack of adequate screening techniques and non-specific symptoms, most women are diagnosed in the advanced stages of the cancer, meaning that the survival rates of ovarian cancer are low in comparison to many other cancers. The 5-year survival rate for women diagnosed with advanced stage ovarian cancer is 18%, compared with a 5-year survival rate of 78% for women diagnosed at an early stage. Furthermore, while most women respond to standard chemotherapy, up to 75% will eventually relapse with recurrent disease.
With the overall goal of improving survival in women with ovarian cancer, our Research Group focuses on two main projects:
- The development of a blood-based DNA test for the early detection of ovarian cancer in high-risk women. We are examining DNA methylation in circulating tumour DNA (ctDNA) from ovarian cancer patients using Next-Generation Sequencing to identify differences in methylation patterns between women with ovarian cancer and control women. The aim is to apply these DNA methylation differences to a blood-based test that can be used in women who are at high-risk for ovarian cancer (e.g. women with a family history or who carry a BRCA1/2 mutation).
- Investigation of novel therapeutic targets in the tumour microenvironment. We focus on Connective Tissue Growth Factor (CTGF), which is currently under investigation as a therapeutic target in pancreatic cancer and other diseases. We have found that CTGF promotes ovarian cancer cell migration and invasion, as well as adhesion to peritoneal surfaces. These effects can be blocked by the addition of a therapeutic monoclonal antibody to CTGF, which is currently in clinical trials in patients with pancreatic cancer.
Warton K, Lin V, Navin T, Armstrong NJ, Kaplan W, Ying K, Gloss B, Mang H, Nair SS, Hacker NF, Sutherland RL, Clark SJ and Samimi G. Methylation-capture and Next-Generation Sequencing of free circulating DNA from human plasma. BMC Genomics 15(1):476, 2014.
Gloss B, Moran-Jones K, Lin V, Gonzalez M, Scurry J, Hacker NF, Sutherland RL, Clark SJ* and Samimi G*. ZNF300P1 Encodes a lincRNA that regulates cell polarity and is epigenetically silenced in type II epithelial ovarian cancer. Mol Cancer 13(1):3, 2014.
Scott CL, Becker MA, Haluska P and Samimi G. Patient-derived xenograft models to improve targeted therapy in epithelial ovarian cancer treatment. Front Oncol 3:295, 2013.
Gloss BS and Samimi G. Epigenetic biomarkers in epithelial ovarian cancer. Cancer Lett 342(2):257–263, 2014.
Yeung TL , Leung C, Dr. Wong K-K, Samimi G, Thompson MS, Liu J, Zaid T, Ghosh S, Birrer MJ and Mok SC. TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res 73(16):5016-5028, 2013.
Samimi G, Ring BZ, Ross DT, Sietz RS, Sutherland RL, O’Brien PM, Hacker NF and Huh WK. TLE3 expression is associated with sensitivity to paclitaxel treatment in ovarian carcinoma. Cancer Epidemiol Biomarkers Prev 21(2):273-279, 2012.
Montavon C, Gloss BS, Warton K, Barton CA, Statham AL, Scurry JP, Tabor B, Nguyen TV, Qu W, Samimi G, Hacker NF, Sutherland RL, Clark SJ, O’Brien PM. Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer. Gynecol Oncol 124(3):582-588, 2012.
Mok SC, Bonome T, Vathipadiekal V, Bell A, Johnson ME, Wong KK, Park DC, Hao K, Yip DK, Donninger H, Ozbun L, Samimi G, Brady J, Randonovich M, Pise-Masison CA, Barrett JC, Wong WH, Welch WR, Berkowitz RS, Birrer MJ. A gene signature predictive for outcome in advanced ovarian cancer identifies a novel survival factor: microfibril-associated glycoprotein 2. Cancer Cell 16(6):521-532, 2009.
Samimi G, Katano K, Holzer AK, Rochdi M, Tomioka M, Goodman M, Safaei R and Howell SB. Increased expression of the copper efflux transporter ATP7A mediates resistance to cisplatin, carboplatin and oxaliplatin in ovarian cancer cells. Clin Cancer Res 10(14):4661-4669, 2004. Cover Article.
Samimi G, Varki NM, Wilczynski S, Safaei R, Alberts DS and Howell SB. Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients. Clin Cancer Res 9(16 pt 1):5853-5859, 2003. Cover Article.
Accompanying Editorial: Kruh GD. Lustrous insights into cisplatin accumulation: copper transporters. Clin Cancer Res 9(16 pt 1):5807-5809, 2003.
Samimi G, Fink D, Varki NM, Husain A, Hoskins WJ, Alberts DS and Howell SB. Analysis of MLH1 and MSH2 expression in ovarian cancer before and after platinum drug-based chemotherapy. Clin Cancer Res 6(4):1415-1421, 2000.
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