In the latter case, aggressive treatment options are avoided. Regarding chemotherapy, adjuvant and neo-adjuvant regimens are used: in an adjuvant chemotherapy regimen, cytostatic drugs are given after a debulking surgery, whereas in a neo-adjuvant setting, cytostatic drugs are given prior to cytoreductive surgery. The intention of adjuvant chemotherapy
is to eliminate remaining tumour cells, thereby, preventing a relapse. Neo-adjuvant chemotherapy aims at reducing the tumour burden before surgery, intending to remove STI571 molecular weight the tumour completely with one large surgery [70]. The crucial step in ovarian carcinoma treatment is the first surgery of the primary tumour, since only this can cure the disease [71]. All regimens applying chemotherapy (at present) are only of palliative value. The current standard chemotherapy comprises a combination of Carboplatin and Paclitaxel. Alternatively, a combination of Carboplatin and Gemcitabine may be used. However, the majority of patients will face relapsed disease. Approximately 20% are Platinum-refractory early relapses with very poor prognosis occuring within the first 6 months after therapy. The remaining 80% are Platinum-sensitive late relapses. In the first case, Topotecan or the antracycline Doxorubicin, masked in liposomes of polyethylenglycol, are considered
as a remaining therapy option. In the latter case (Platinum-sensitive relapse) a Carboplatin/Paclitaxel doublet remains first choice chemotherapy. www.selleckchem.com/products/ch5183284-debio-1347.html Therapy of relapsed ovarian cancer always is of palliative this website nature, thus, intending to delay disease progression, reduce pain, and maintain quality of life [67]. Clinical findings show that the development of resistance to therapy of ovarian cancer is a time-dependent biological process [65]. In our study we used A2780 epithelial ovarian
cancer cells as a model system to investigate the molecular determinants of Cisplatin resistance and uncovered the molecular mechanism of action. Since A2780 is not a representative cell line for the most common histology subtype of epithelial ovarian cancer, we generalized our findings by analysing also HEY, OVCAR-8, SKOV-3, Phosphoribosylglycinamide formyltransferase and BG-1 cell lines. In addition, a clinical trial with 80 ovarian cancer tumour samples was analysed. To mimic the clinical situation of Cisplatin therapy in vitro, we followed the same procedure as with MCF-7 breast cancer cells: we generated Cisplatin-resistant cells by weekly cycles of Cisplatin at a dose, which is reached in patients in the clinic and assessed the emergence of resistance during 6 months. We found a correlation of increasing IGF-1R mRNA expression levels with the emergence of resistance to Cisplatin. In order to analyse generalisability of this finding, we correlated IGF-1R mRNA expression with the intrinsic Cisplatin resistance status in a panel of human ovarian cancer cells and found a significant correlation [72].