Other regimens that showed objective response included irinotecan

Other regimens that showed objective response included irinotecan/platinum, etoposide/platinum, and paclitaxel/carboplatin;

however, the efficacy was limited with progression-free interval approximately 6 months. Despite importance of response, it would be more important to monitor if adverse effects of chemotherapy worsen quality of life of the patients. Among these PF-02341066 ic50 reports, the longest progression-period of 14 months was obtained by Temsirolimus [47]. The observed response duration was surprisingly longer than those obtained by any cytotoxic agents so far with no serious toxicities. The report encouraged us to investigate another chemotherapeutic strategy for CCC. From the reported cases, however, it could be concluded that CCC is a potentially extremely chemo-resistant tumor against cytotoxic agents, especially in recurrent or refractory settings. Another strategy including molecular PD0332991 supplier targeting agents might be needed for the treatment of these tumors. Incorporation of molecular targeting agents for the treatment of CCC In the aspects of molecular characteristics as well as clinical behavior, it is hypothesized that CCC belongs

to a different entity from other histological subtypes of ovarian carcinoma. First of all, the incidences of p53 mutation and p53 overexpression were much less frequent in CCC than in other histologic types of epithelial ovarian cancer [49, 50]. On the DNA Damage inhibitor other hand, mutation of p53 gene was quite frequent in serous subtype of ovarian cancers, and most of the alterations were missense mutations [51]. In addition

to p53 status, CCC has a quite unique expression pattern of several molecules. Glutathione Cytidine deaminase peroxidase 3 (GPX3) was found at levels 30-fold higher on average in CCC compared with the other ovarian cancer subtypes through studies with cDNA arrays and serial analysis of gene expression [52]. Elevated expression of GPX3 might contribute to chemoresistance phenotype, which is often observed in the patients with CCC. Another investigation using oligonucleotide microarrays reported that glutaredoxin (GLRX) and superoxide dismutase 2 (SOD2), in addition to GPX3, were highly expressed in clear cell type ovarian cancer, suggesting that high levels of these proteins relating with antioxidant function render CCC to be more resistant to chemotherapy [53, 54]. Further, a report using oligonucleotide probe arrays showed that a transcription factor, hepatocyte nuclear factor-1 (HNF-1) was upregulated in CCC cell lines [55]. Overexpression of HNF-1 was confirmed by immunohistological staining of clinical samples. Further, overexpression of HNF-1 was observed in the specimens of borderline clear cell tumor and benign clear cell tumor [56].

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