On-target inhibition of tumor fermentative glycolysis as visualized by hyperpolarized pyruvate.

摘要: Many cancer cells display the Warburg effect, that is, enhanced glycolysis followed by fermentation (conversion of pyruvate to lactate). Recently, molecular basis for these effects has started be elucidated, and upregulation lactate dehydrogenase A (LDH-A) isoform is felt a major mediator this phenomenon. Moreover, LDH-A expression in tumor tissue levels blood portend bad prognosis, blockade can lead growth inhibition transplant models. We have extended existing data (some which were published during time when we carrying out our studies) two important ways: 1) glycolytic lung cell line results reactive oxygen species– mediated apoptosis increased sensitivity chemotherapeutic drug paclitaxel 2) fermentative also accomplished activation complex dichloroacetate, now undergoing clinical trials, phenomenon monitored vivo noninvasive real-time manner through magnetic resonance spectroscopy using hyperpolarized pyruvate. Collectively, suggest drugs redirect fate pyruvate, hence are aimed at reversing could use spectroscopy, method scalable human use.