Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer

被引：102

作者：

Nayak, Amruta P. ^{[1
,2
]}

Kapur, Arvinder ^{[2
]}

Barroilhet, Lisa ^{[2
]}

Patankar, Manish S. ^{[2
]}

机构：

[1] Indian Inst Sci Educ & Res, Pune 411008, Maharashtra, India

[2] Univ Wisconsin Madison, Dept Obstet & Gynecol, Madison, WI 54911 USA

来源：

CANCERS | 2018年 / 10卷 / 09期

关键词：

high grade serous ovarian cancer; metabolism; mitochondria; oxidative phosphorylation; oxidative stress; biguanides; atovaquone; plumbagin; thiazolidinediones; ubiquinone; Nrf-2; OLAPARIB MAINTENANCE THERAPY; GRADE SEROUS CARCINOMA; PYRUVATE-KINASE M2; INTRAEPITHELIAL CARCINOMA; TP53; MUTATIONS; CYTOCHROME-B; COMPLEX I; TUMORS; CELLS; METABOLISM;

D O I：

10.3390/cancers10090337

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies to interfere with oxidative phosphorylation should be considered for the treatment of ovarian tumors. Here, we review the literature that supports this hypothesis and describe potential agents and critical control points in the oxidative phosphorylation pathway that can be targeted using small molecule agents. In this review, we also discuss potential barriers that can reduce the efficacy of the inhibitors of oxidative phosphorylation.

引用

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