The “Sweet Spot” of Targeting Tumor Metabolism in Ovarian Cancers
Abstract
Simple Summary
Abstract
1. Introduction
2. Metabolomic Alterations in Ovarian Cancer
2.1. Glycolysis
2.2. Altered Fatty Acid Metabolism
2.3. Oxidative Phosphorylation
2.4. Hypoxia-Induced Factor
2.5. Leptin
2.6. Insulin-like Growth Factor Binding Proteins
3. Signaling Pathways
3.1. PI3K/AKT/mTOR
3.2. JAK/STAT
4. Targeted Therapies in Ovarian Cancer
Targeted Pathway | Specific Agent or Compound Name | Trial Phase | Findings/Summary | Study or Trial Number |
---|---|---|---|---|
Glycolysis | miR-206, miR-613 | Preclinical | G6PD inhibitors, miR-206, and miR-613 sensitize resistant cells to cisplatin. | Zheng et al. [65] |
GLUT1 inhibitor BAY-876 | Preclinical | Targeting of GLUT1 suppresses glycolytic metabolism and in vitro and in vivo ovarian cancer growth. | Ma et al. [12] | |
Metformin | Clinical trial | Role of combining carboplatin, paclitaxel, and metformin in advanced stage ovarian cancer. Study is ongoing. | NCT02437812; Brown et al. [75] | |
Fatty acid metabolism | FASN inhibitor Compound 34 | Preclinical | Compound 34 inhibits cell proliferation in multiple cancer cell lines including ovarian, prostate, lymphoma, lung, and breast. | Lu et al. [76] |
FASN inhibitor cerulenin | Preclinical | FASN inhibitor cerulenin strongly blocked FASN protein expression and both stimulated apoptosis and re-induced platinum sensitivity. | Bauerschlag et al. [77] | |
Oxidative phosphorylation | Respiratory chain complex I inhibitor IACS-010759 | Preclinical | Inhibitor caused mitochondrial swelling and ATP depletion to delay cancer progression and prolonged the lifespan of ovarian cancer PDX tumors. | Ghilardi et al. [78] |
Hypoxia | 2-Methoxyestradiol (2ME2) | Phase II clinical trial, completed | 2ME2 is an endogenous metabolite of estradiol that destabilizes microtubules and exerts anti-angiogenic properties; 31.3% clinical benefit rate in ovarian cancer. | Matei et al. [74] |
Camptothecin nanoparticle-drug conjugate (NLG207/CRLX101/EP0057) | Phase Ib/II clinical trial, completed | HIF-1α inhibition in combination with weekly paclitaxel yielded 31.6% overall response rate. | NCT02389985 | |
EP0057, a nanoparticle-drug conjugate (NDC) of camptothecin | Clinical trial | EP0057 in combination with olaparib in ovarian cancer. Study is ongoing. | NCT04669002 | |
PI3K/AKT/ mTOR | Oral AKT inhibitor GSK2141795 | Clinical trial | Pharmacokinetics and pharmacodynamics study in ovarian cancer patients. Study is ongoing. | NCT01266954 |
Oral PI3K inhibitors BKM120 or BYL719 | Phase I clinical trial | PI3 kinase inhibition in combination with olaparib. | NCT01623349 | |
Oral PI3K inhibitor BKM120 | Phase I clinical trial | Safety of BKM120 monotherapy in advanced solid tumors. | NCT01068483 | |
JAK/STAT | JAK2-specific inhibitor CYT387 | Preclinical | CYT387 in combination with paclitaxel resulted in the suppression of JAK2/STAT3 activation, which coincided with significantly smaller tumors in mice. | Abubaker et al. [68] |
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Tondo-Steele, K.; McLean, K. The “Sweet Spot” of Targeting Tumor Metabolism in Ovarian Cancers. Cancers 2022, 14, 4696. https://doi.org/10.3390/cancers14194696
Tondo-Steele K, McLean K. The “Sweet Spot” of Targeting Tumor Metabolism in Ovarian Cancers. Cancers. 2022; 14(19):4696. https://doi.org/10.3390/cancers14194696
Chicago/Turabian StyleTondo-Steele, Katelyn, and Karen McLean. 2022. "The “Sweet Spot” of Targeting Tumor Metabolism in Ovarian Cancers" Cancers 14, no. 19: 4696. https://doi.org/10.3390/cancers14194696
APA StyleTondo-Steele, K., & McLean, K. (2022). The “Sweet Spot” of Targeting Tumor Metabolism in Ovarian Cancers. Cancers, 14(19), 4696. https://doi.org/10.3390/cancers14194696