The goal of our laboratory is to identify the mechanisms underlying the association of systemic metabolism and cancer, particularly that of the lung, pancreas and colon.
Evidence for a robust correlation between systemic metabolism and cancer incidence and progression has been accumulating for over a century. Indeed, the anti-tumorigenic effects of dietary restriction that are known to delay cancer incidence and decrease tumor growth in laboratory rodents, have been recognized since the early 1900s. Moreover, the last quarter of the twentieth century has witnessed a worldwide epidemic surge of obesity and its associated metabolic syndrome (dyslipidemia, hypertension, hyperglycemia, insulin resistance and type2 diabetes). Recent epidemiological studies demonstrate a linear correlation between the observed increase in obesity as well as type2 diabetes and mortality from cancers of a wide variety of tissues. This correlation has been estimated to account, in the United States, for 14% and 20% of all deaths from cancer in men and women, respectively.
Our recent work has unveiled a key role for the PTEN/PI3K pathway in determining tumor sensitivity to dietary restriction at early stages of tumor formation. This signaling pathway, known to integrate extracellular hormonal/growth factor stimuli to regulate cell survival, proliferation, and motility, is frequently mutated in a broad array of human cancers and has therefore been extensively studied. However, the role of PTEN/PI3K pathway in modulating the response of tumors to body metabolism is just starting to emerge.
Our laboratory aims at understanding how signaling pathways, such as PI3K/PTEN, influence tumor initiation and maintenance in the context of obesity and its metabolic syndrome and whether such an effect can be exploited therapeutically.