In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival

Abstract

Background:Carboplatin and cisplatin, alone or in combination with paclitaxel, have similar efficacies against ovarian cancer (OVCA) yet exhibit different toxicity profiles. We characterised the common and unique cellular pathways that underlie OVCA response to these drugs and analyse whether they have a role in OVCA survival.Methods:Ovarian cancer cell lines (n=36) were treated with carboplatin, cisplatin, paclitaxel, or carboplatin–paclitaxel (CPTX). For each cell line, IC50 levels were quantified and pre-treatment gene expression analyses were performed. Genes demonstrating expression/IC50 correlations (measured by Pearson; P<0.01) were subjected to biological pathway analysis. An independent OVCA clinico-genomic data set (n=142) was evaluated for clinical features associated with represented pathways.Results:Cell line sensitivity to carboplatin, cisplatin, paclitaxel, and CPTX was associated with the expression of 77, 68, 64, and 25 biological pathways (P<0.01), respectively. We found three common pathways when drug combinations were compared. Expression of one pathway (‘Transcription/CREB pathway') was associated with OVCA overall survival.Conclusion:The identification of the Transcription/CREB pathway (associated with OVCA cell line platinum sensitivity and overall survival) could improve patient stratification for treatment with current therapies and the rational selection of future OVCA therapy agents targeted to these pathways.

Platinum Compounds for High‐Resolution In Vivo Cancer Imaging

“…Although the carboplatin-related compound CP- 6 was less potent than CP- 11 , it only exhibited a 1.3-2.7 fold loss in potency compared to its parent drug carboplatin, depending on the cell line (Table 1). Of note, carboplatin sensitivity observed here is highly consistent with previously published results [25] .…”

Neo-adjuvant chemotherapy does not increase the rate of complete resection and does not significantly reduce the morbidity of Visceral–Peritoneal Debulking (VPD) in patients with stage IIIC–IV ovarian cancer

“…It is still debated in the literature whether the CR following chemotherapy holds the same value of the CR achieved after primary surgery. Many authors suggest a disease-concealing role exerted by the neo-adjuvant chemotherapy [15][16][17][18][19][20][21]. This could disguise the real extent of disease and curtail the aggressiveness of the surgery [18].…”

Analysis of Chemotherapeutic Response in Ovarian Cancers Using Publicly Available High-Throughput Data

“…that controls vesicle traffic within the cell (27) and members of the RAS oncogene family (11,28), MAPK14 and PDGFD (29) part of the MAPK signaling pathway (P ¼ 10 À4 ), involved in the initiation of a G 2 delay after UV radiation (30) and also identified in in vitro studies (11). Only these candidate pathways, previously associated with chemoresponse, were used in the rest of the study.…”

“…In previous studies, we have identified a series of molecular signaling pathways associated with OVCA response to chemotherapy in vitro as well as in clinical settings (10)(11)(12)(13). We selected pathways associated with chemoresponse to design a pilot study aimed to identify biologic processes that influence expression.…”