Romero Research Program: Drug Repurposing
With the goal of increasing access to treatment, Dr. Romero’s ovarian cancer research program utilizes an approach called drug repurposing. Her group focuses their efforts on inexpensive, safe, widely used compounds that have anti-neoplastic effects and are already approved by the Food and Drug Administration (FDA) for non-cancer indications.
Over the past 14 years, Dr. Romero’s research group integrated in vitro cancer biology techniques, mouse models of cancer, and human clinical data and biospecimens to identify novel anti-cancer effects of commonly used drugs. Dr. Romero’s work added to an increasing number of studies indicating that medications that are commonly used for non-cancer indications have the potential to be repurposed as therapeutics targeted against cancer cell metabolism.
- Romero IL, Lee W, Mitra AK, Gordon IO, Zhao Y, Leonhardt P, Penicka CV, Mui KL, Krausz TN, Greene GL, and Lengyel E. The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis. Gynecology Oncology, 2012 Jan;124(1):134-41. PMID: 21996264.
- Romero IL, McCormick A, McEwen KA, Park S, Karrison T, Yamada SD, Pannain S, and Lengyel E. Relationship of type II diabetes and metformin use to ovarian cancer progression, survival and chemosensitivity. Obstetrics and Gynecology. 2012 Jan;119(1):61-7. PMID: 22183212.
- Habis M, Wroblewski K, Bradaric M, Ismail N, Litchfield L, Lengyel E, and Romero IL. Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: A retrospective cohort analysis. PLOS One. 2014 Aug 13;9(8):e104521. PMID: 25118694.
- Lengyel E, Litchfield LM, Mitra AK, Nieman KM, Mukherjee A, Zhang Y, Johnson A, Bradaric M, Lee W, and Romero IL. Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models. American Journal of Obstetrics and Gynecology. 2015 April;212(4):479. PMID: 25446664.
- Litchfield LM, Johnson A, Mills KA, Pan S, Shridhar V, Lengyel E, and Romero IL. Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer. Oncotarget. 2015 Sept 15;6(27):23548-60. PMID: 26172303.
- Ozewuiro O, Grushko TA, Kocherginsky M, Habis M, Olopade OI, Hurteau JA, Mills KA, Hunn J, Fleming GF, and Romero IL. Association of metformin use and outcomes in advanced endometrial cancer treated with chemotherapy. PLoS One.2016 Jan 20:11(1):e0147145. PMID: 26788855.
- Liu X, Romero IL, Litchfield LM, Lengyel L, and Locasale JW. Metformin targets tumor central carbon metabolism and reveals mitochondrial requirements in human cancers. Cell Metabolism. 2016 Nov 8;24(5):728-739. PMID: 27746051.
- Chiyoda T, Hart PC, Eckert MA, McGregor SM, Lastra RR, Hamamoto R, Nakamura Y, Yamada SD, Olopade OI, Lengyel E, and Romero IL. Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention. Cancer Prevention Research. 2017 Apr 10(4):255-266. PMID: 2826438.
- Hart PC, Chiyoda T, Liu X, Weigert M, Curtis M, Chang CY, Loth R, Lastra R, McGregor SM, Locasale JW, Lengyel E, and Romero IL. SPHK1 is a novel target of metformin in ovarian cancer. Molecular Cancer Research. 2019 April; 17(4):870-881. PMID: 30655321.
- Hart PC, Kenny HA, Grassl N, Watters KM, Litchfield LM, Coscia F, Blaženović I, Ploetzky L, Fiehn O, Mann M, Lengyel E, and Romero IL. Mesothelial cell HIF1α expression is metabolically downregulated by metformin to prevent oncogenic tumor : stroma crosstalk. Cell Reports 2019 Dec 17;29(12):4086-4098. PMID: 31851935.
- Strohsnitter WC, Hyer M, Bertrand KA, Cheville AL, Palmer JR, Hatch EE, Aagaard KM, Titus L, Romero IL, Huo D, Hoover RB, and Troisi R. Prenatal diethylstilbestrol exposure and cancer risk in males. Cancer Epidemiology Biomarkers & Prevention. 2021 Oct 1;30(10):1826-1833. PMID: 34272263.
- Febbrarro T, Lengyel E, and Romero IL. Old drug, new trick: Repurposing metformin for gynecologic cancers? Gynecology Oncology. 2014 Dec; 135(3):614-621. PMID: 25455733.
- Romero IL, Mukherjee A, Kenny HA, Litchfield LM, and Lengyel E. Molecular Pathways: Reciprocal regulation of cancer and stromal cells. Clinical Cancer Research. 2015 Feb 15; 21(4)680-6. PMID: 25691772.