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

Hiroshi Kobayashi, Hiroshi Shigetomi, Chiharu Yoshimoto
Oncology letters · 2015 · vol. 10(2) , pp. 571–576 · doi:10.3892/ol.2015.3268 · PMID:26622535 · PMC4508996 · W1567760134
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review identifies elevated hepatocyte nuclear factor-1β as a potential driver of chemoresistance in clear cell ovarian carcinoma by affecting cell cycle checkpoints, suggesting Chk1 inhibitors as a targeted therapy.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This paper reviews English-language studies (2000–2014) to examine how the transcription factor hepatocyte nuclear factor (HNF)-1β may connect with cell cycle checkpoint machinery and chemoresistance in ovarian clear cell carcinoma, using literature on genomic alterations and aberrant pathways. It highlights that oxidative stress linked to repeated hemorrhage in endometriotic lesions can increase DNA damage, and that in clear cell carcinoma HNF-1β–associated checkpoint kinase 1 (Chk1) shows persistent phosphorylation with resulting G2/M arrest; HNF-1β deletion is reported to induce apoptosis. The caveat is that it is a narrative review with no new experimental data, focusing on synthesizing previously reported mechanisms rather than establishing clinical efficacy. This paper is centrally about endometriosis-associated ovarian clear cell carcinoma—specifically, it discusses HNF-1β and Chk1 as mechanistic links between endometriosis-related oxidative stress and clear cell carcinoma chemoresistance.

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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.

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Condition tags

endometriosis

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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chemicals 3
heme iron platinum

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