Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors
Karen E Sheppard, Carleen Cullinane, Katherine M Hannan, Meaghan Wall, Joanna Chan, Frances Barber, Jung Foo, Donald Cameron, Amelia Neilsen, Pui Ng, Jason Ellul, Margarete Kleinschmidt, Kathryn M Kinross, David D Bowtell, James G Christensen, Rodney J Hicks, Ricky W Johnstone, Grant A McArthur, Ross D Hannan, Wayne A Phillips Show all
EUROPEAN JOURNAL OF CANCER | ELSEVIER SCI LTD | Published : 2013
BACKGROUND: Ovarian cancer is the major cause of death from gynaecological malignancy with a 5year survival of only ∼30% due to resistance to platinum and paclitaxel-based first line therapy. Dysregulation of the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) and RAS/extracellular signal-regulated kinase (ERK) pathways is common in ovarian cancer, providing potential new targets for 2nd line therapy. METHODS: We determined the inhibition of proliferation of an extensive panel of ovarian cancer cell lines, encompassing all the major histotypes, by the dual PI3K/mTOR inhibitor PF-04691502 and a MEK inhibitor, PD-0325901. In addition, we analysed global gene expression, mut..View full abstract
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Awarded by NHMRC of Australia
The authors thank Jeannette Schreuders, Susan Jackson and Ekaterina Bogatyreva for technical assistance. This work was supported by grants from the NHMRC of Australia to KES and RBP (#I043884), RWJ (#251608 and #566702), GAM (#400120 and#566876), RDH (#166908 and #251688), WAP (#628620), RBP (#509087 and #400116) and from Pfizer Oncology. Researchers were funded by NHMRC (Research Fellowships to RWJ, RDH and RBP) and Cancer Council of Victoria (Sir Edward Weary Dunlop Fellowship to GAM).