Early Detection of Lung Cancer
Lung cancer is the most lethal cancer, killing ~1.3 million people worldwide every year. Early diagnosis could increase its survival by 3-4 folds. Expected survival is greater than 70% if the cancer is discovered in early stage. The recent NLST trial has shown that annual CT scans for risk cohort can reduce the lung cancer related mortality by 20%. Therefore the yield of screening for lung cancer is not a question anymore and the urgent unmet need is to define the group that is under a high risk for lung cancer. Our lab is focusing on revealing non-invasive biomarkers as for early detection of lung cancer.
Specifically, we are performing exhaled breath nano-analysis in collaboration with Prof. Hossam Haick from the Technion Institute. Our recent studies report a noninvasive and highly sensitive test, based on detecting characteristic volatile organic compounds (VOCs) from exhaled breaths (eNose) and from the headspace of cancerous cell lines. In addition, detecting of circulating molecular biomarkers using a simple blood test could easily assist it early diagnosis of lung cancer.
It is expected that molecular biology and gene technologies offer some of the most promising tools to identify biomarkers for early detection of lung cancer, and biomarkers discovered by molecular methods will be translated to more readily obtainable biologic samples (blood and sputum) that would be applicable to large-scale cost effective screening in high-risk groups. The characterization of the multistep molecular alterations in lung cancer pathogenesis could provide better candidate biomarkers for early diagnosis.
Effective diagnostic tools for screening and early detection of lung cancer would have many beneficial advantages including primarily enhanced detection of lung cancer in its early stages allowing earlier and curative therapy for more patients with the disease. These new concepts based on volatile compounds and circulating molecular biomarkers have the potential to reduce cancer mortality, by enabling widespread, constant screening, especially for high-risk populations, through a non-invasive test or minimally invasive procedures.
Metabolic Modification as a Potential Therapeutics Approach in Lung Cancer
It is well established that cancer cell can activate their glycolysis pathway in order to survive in hypoxia micro-environment. Tumors cells show a high rate of glycolysis and lactate production, even in the presence of oxygen. Importantly, some cancer cells demonstrate impaired mitochondria respiration and high glycolysis, namely Warburg effect. It is known that most types of cancers fit the “Warburg hypothesis” because a decreased expression of mitochondrial ATP synthase, which is a bottleneck of mitochondrial oxidative phosphorylation. Warburg Effect as a target for therapy can be achieved by a small molecule, e.g. dichloroacetate (DCA). DCA inhibits the pyruvate dehydrogenase kinase (PDK), thus increases the flux of pyruvate into the mitochondria, and therefore promoting mitochondrial activation.Our overall goal is to target Warburg phenomenon as a treatment approach for lung cancer and to reverse the metabolic activity towards its normal glycolysis/mitochondrial ratio. Glycolysis shut-down and mitochondrial activation induce cell death in lung cancer cell lines. This can serve as a basis for further understanding the role of glycolytic phenotype mechanism in lung cancer. Our research is a proof of concept for the feasibility of metabolic modification to treat lung cancer.