Warburg science goes to the bedside: A phase I trial of 2-deoxyglucose in patients with prostate cancer and advanced malignancies
| Autor: | Robert S. DiPaola, M. N. Stein, Weichung Joe Shih, Dmitri Dvorzhinski, S. Doyle-Lindrud, Eileen White, Susan Goodin, Stephanie Beers, Simantini Eddy, Eric H. Rubin |
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| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 26:16087-16087 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2008.26.15_suppl.16087 |
| Popis: | 16087 Background: A profound, but therapeutically unexploited, difference between cancer and normal tissues is the preferential utilization of glycolysis (the ‘Warburg effect‘) for energy by cancer cells. Additionally, similar to mechanisms of chemotherapy resistance, potential mechanisms of cancer cell resistance to starvation have recently emerged. One pathway by which cells survive periods of metabolic stress is thought to be autophagy, which is a catabolic process of organelle digestion that creates ATP during periods of nutrient limitation and is regulated by the protein Beclin1. Methods: We developed this novel paradigm in pre-clinical models and a phase I clinical trial. Preclinically, we used immortalized mouse epithelial prostate cells, as well as PC-3 and LNCaP cell lines, and a transfected pEGFP-LC3 autophagy marker construct to assess cytotoxicity and autophagy induction by 2-deoxyglucose (DG). In the clinic, eligible patients receive DG orally on days 1–14 of a 21 day cycle in cohorts of 3 in... |
| Databáze: | OpenAIRE |
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