Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling.
The purpose of this study was to investigate a new modality of therapy against ovarian clear cell carcinoma (OCCC), a chemoresistant subtype of ovarian cancer. Microarray datasets of ovarian cancer cell lines and cancer tissues were analyzed using bioinformatic tools. The gene expression profile of OCCC was similar to that of renal cell carcinoma (RCC). This similarity was at least partially due to hepatocyte nuclear factor 1 pathway activation common to both malignancies. In addition, oncogenic pathway alterations were characteristic of OCCC including hypoxia inducible factor 1 alpha subunit and relatively high Ras activities. Therefore, we predicted that the multi-kinase inhibitor sorafenib, which is approved for RCC and suppresses Ras activity, would also be effective against OCCC. Orally administered sorafenib (40 mg/kg per day) significantly inhibited tumor growth in nude mice when it was given after inoculation with the OCCC cell line RMG-2 (P = 0.002). Furthermore, sorafenib significantly reduced tumor size when it was administered to established RMG-2 tumors (P = 0.0002), while intraperitoneal injection of cisplatin (5 mg/kg per week) did not. In conclusion, the prominent anti-tumor effect of sorafenib against OCCC indicates that sorafenib is a promising candidate drug and supports the need for clinical trials using sorafenib against OCCC. This report demonstrates a method to utilize genome-wide information to facilitate translational research for treatments against less common subtypes of cancers.
Matsumura, N; Mandai, M; Okamoto, T; Yamaguchi, K; Yamamura, S; Oura, T; Baba, T; Hamanishi, J; Kang, HS; Matsui, S; Mori, S; Murphy, SK; Konishi, I
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