Checkpoint kinase 1 inhibitors as targeted molecular agents for clear cell carcinoma of the ovary (Review)

  • Authors:
    • Hiroshi Kobayashi
    • Hiroshi Shigetomi
    • Chiharu Yoshimoto
  • View Affiliations

  • Published online on: May 26, 2015     https://doi.org/10.3892/ol.2015.3268
  • Pages: 571-576
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In clear cell carcinoma of the ovary, chemoresistance frequently results in treatment failure. The present study aimed to review the potential association of transcription factor hepatocyte nuclear factor (HNF)-1β with cell cycle checkpoint machinery, as a mechanism for chemoresistance. The English-language literature on the subject was reviewed to identify genomic alterations and aberrant molecular pathways interacting with chemoresistance in clear cell carcinoma. Oxidative stress induced by repeated hemorrhage induces greater susceptibility of endometriotic cells to DNA damage, and subsequent malignant transformation results in endometriosis-associated ovarian cancer. Molecular changes, including those in HNF-1β and checkpoint kinase 1 (Chk1), may be a manifestation of essential alterations in cell cycle regulation, detoxification and chemoresistance in clear cell carcinoma. Chk1 is a critical signal transducer in the cell cycle checkpoint machinery. DNA damage, in turn, increases persistent phosphorylation of Chk1 and induction of G2/M phase cell cycle arrest in cells overexpressing HNF-1β. HNF-1β deletion induces apoptosis, suggesting that enhanced levels of HNF-1β may be associated with chemoresistance. Targeted therapy with Chk1 inhibitors may be explored as a potential treatment modality for patients with clear cell carcinoma. This provides a novel direction for combination therapy, including targeting of Chk1, which may overcome drug resistance and improve treatment efficacy.
View Figures
View References

Related Articles

Journal Cover

August-2015
Volume 10 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kobayashi H, Shigetomi H and Yoshimoto C: Checkpoint kinase 1 inhibitors as targeted molecular agents for clear cell carcinoma of the ovary (Review). Oncol Lett 10: 571-576, 2015.
APA
Kobayashi, H., Shigetomi, H., & Yoshimoto, C. (2015). Checkpoint kinase 1 inhibitors as targeted molecular agents for clear cell carcinoma of the ovary (Review). Oncology Letters, 10, 571-576. https://doi.org/10.3892/ol.2015.3268
MLA
Kobayashi, H., Shigetomi, H., Yoshimoto, C."Checkpoint kinase 1 inhibitors as targeted molecular agents for clear cell carcinoma of the ovary (Review)". Oncology Letters 10.2 (2015): 571-576.
Chicago
Kobayashi, H., Shigetomi, H., Yoshimoto, C."Checkpoint kinase 1 inhibitors as targeted molecular agents for clear cell carcinoma of the ovary (Review)". Oncology Letters 10, no. 2 (2015): 571-576. https://doi.org/10.3892/ol.2015.3268