Pre-clinical analysis of therapies targeted to specific sub-types of epithelial ovarian cancer
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Stem Cells and Cancer | .(JavaScript must be enabled to view this email address) |
Dr Matthew Wakefield (Co-supervisor) |
Bioinformatics | .(JavaScript must be enabled to view this email address) |
Details of project
We are developing novel mouse models of high-grade serous ovarian cancer (HG-SOC) and classifying the HG-SOC according to important features such as DNA repair capability, response to platinum chemotherapy and PARP inhibitors and Tothill sub-type (Tothill et al Clin Canc Res 2008).
Novel treatments will be targeted to HG-SOC of the relevant phenotype, in whole mouse models, to improve molecular understanding of drug response. Mouse models allow us to look at how the tumour responds to treatment and provide experimental flexibility not possible with either established human cells or analysis of patient tumour samples.
Improved pre-clinical mouse models will enhance our ability to use molecular approaches to devise and test new therapeutic strategies for ovarian cancer.
Project references
- Tothill RW, Tinker AV, George J, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008 14;5198-5208.
- Helland A, Anglesio MS, George J et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS One. 2011 Apr 13;6(4).
- The Cancer Genome Atlast Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 474;609-615.
Research interests
Ovarian cancer is the fifth major cause of cancer mortality in women. Usually presenting at late clinical stage due to the difficulty of early diagnosis, ovarian cancer is often drug resistant. The most lethal type is high-grade serous epithelial ovarian cancer. We are interested in developing therapies targeting defects in cell signalling in newly described sub-sets of high-grade serous epithelial ovarian cancer.
Selected publications
- Cragg MS, Jansen ES, Cook M, Harris C, Strasser A and Scott CL. Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic. J Clin Invest. 2008 118;3651-3659.
- Cragg MS, Harris C, Strasser A and Scott CL. Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat Rev Cancer. 2009 9;321-326.
- Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 376;245-251.
- Domchek SM, Mitchell G, Lindeman GL, Tung N, Balmaña J, Isakoff SJ, Schmutzler R, Audeh MW, Loman N, Scott CL, Friedlander M, Kaufman B, Garber J, Tutt A, Robson M, BRCA Targeted Therapies Consortium (BRCATAC). Challenges to the development of new agents for molecularly defined patient subsets: lessons from BRCA1/2-associated breast cancer. Journal of Clinical Oncology. In Press. 12 July 2011.
- Chionh F, Mitchell G, Lindeman GJ, Friedlander M and Scott CL. The role of poly adenosine diphosphate ribose polymerase inhibitors in breast and ovarian cancer: Current status and future directions. Asia-Pac J Clin Oncol. In Press. 12 July 2011.
Research theme
Cancer
Scientific discipline
- Cell Biology
- Genetics
- Pathology
Keywords
ovarian cancer, DNA repair, PARP inhibitors, mouse models