Targeting Lung Cancer Vulnerabilities

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SUMMARY Summary of Funded Parent Award and Project. The overall goal of the parent project, 5P50CA070907-23 (The University of Texas SPORE in Lung Cancer, “Targeting Lung Cancer Vulnerabilities”) is to identify liabilities in human lung cancer, understand the mechanistic basis of these vulnerabilities and develop therapeutic strategies that can be deployed in patients. Dr. DeBerardinis leads Project 1: “Targeting Metabolic Vulnerabilities in Lung Cancer.” The central hypothesis of this Project is that metabolic phenotypes in human non-small cell lung cancer (NSCLC) can provide a source of new therapeutic targets and biomarkers that predict therapeutic sensitivities and clinical outcomes. The Project uses a state-of-the-art approach to assess metabolism of human lung tumors using stable isotope tracers. In this approach, patients with solitary pulmonary nodules are recruited to a clinical protocol (NCT01668082) and intravenously infused with 13C-glucose during surgical resection of the tumor and adjacent lung. Metabolites extracted from tissue samples procured by the surgeon are then assessed by mass spectrometry to compare 13C labeling between tumor and adjacent, nonmalignant lung. We have used this approach to assess the causes of metabolic heterogeneity among tumors, identify metabolic fuels consumed by human tumors in vivo and correlate the metabolic properties of tumors with clinical markers including FDG-PET signal and outcomes1-3.