Redox-Active Iron-Induced Oxidative Stress in the Pathogenesis of Clear Cell Carcinoma of the Ovary

Abstract

These aspects of reactive oxygen species biology will be discussed in the context of its relationship to EAOC carcinogenesis.

Identification of multiple pathways involved in the malignant transformation of endometriosis (Review)

“…In general, hemochromatosis, chronic viral hepatitis, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis or asbestosis induce iron overload, which may lead to hepatocellular carcinoma, colon cancer or mesothelioma in humans (69). Several investigators have demonstrated that iron-induced oxidative stress is also able to induce specific gene modifications in endometriosis-associated ovarian cancer (27,28,(71)(72)(73)(74). Undefined molecular events occurring in endo metriosis that has undergone Müllerian metaplasia may initiate neoplastic change towards not only carcinoma, but also sarcoma.…”

Targeted molecular therapies for ovarian cancer: An update and future perspectives (Review)

“…The integration of this study successfully identifies a set of candidate susceptibility genes for HNF-1β. The preliminary data showed that Chk1 protein is persistently activated in the HNF-1β-overexpressing CCC cells (64). Clinically, relevant drugs targeting proteins connected in the HNF-1β network may be the Chk1 inhibitors.…”

“…Chk1 might function in the cellular survival pathways that enhance DNA damage repair, thereby granting chemoresistance. Chk1 inhibition selectively chemosensitizes HNF-1β-overexpressing CCC cells in vitro (64). The Chk1 inhibitor might be a novel target for developing cancer therapeutics in the HNF-1β-positive cells that can potentially enhance the sensitivity to chemotherapeutic agents acting via induction of DNA damage and apoptosis.…”

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

“…Clear cell carcinoma and endometrioid adenocarcinoma exhibit distinct clinicopathological features and molecular phenotypes (19,20). Yamada et al (21) hypothesized that heme and iron-induced signals contribute to carcinogenesis via three major mechanisms: i) By enhancing oxidative stress, which promotes DNA mutagenesis and contributes to tumor initiation; ii) via activation of detoxification pathways, thereby contributing to tumor promotion; iii) by sustaining growth of cancer cells via estrogen-dependent (endometrioid) or -independent (clear cell) mechanisms. These studies provide novel insights into the pathophysiology and significance of genetic functional categories in EAOC.…”