Recent Developments in Cancer Metabolism

Giuseppe Lonetto

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

Giuseppe Lonetto, Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Keywords: Cancer Metabolism; Heterogeneity; Pancreatic Tumors; Genetic Mutations

Abstract

To identify metabolic vulnerabilities in cancer is of a major importance to better understand the dependence of cancer cells on certain metabolic rewiring, and thus to identify new therapeutic targets. The majority of data provided in the past years relied on in vitro studies. Yet, to reach clinically effective conclusions there is a strong need for powerful systems that recapitulate the complexity of the in vivo environment. Notable examples that qualitatively changed the state of art are recent studies that highlighted the vast cancer metabolic heterogeneity in the in vivo environment, and the poor correlation between data observed in in vivo versus in vivo conditions [1,2]. Just to mention other relevant facts, the role of anaplerotic glutamine addiction was indeed shown to be overrated in culture conditions. It seems, in fact, that pyruvate carboxylation can support anaplerosis better than glutamine [3,4] and that in vivo, glutamine poorly contributes to TCA cycle in mouse lung tumors [1]. Considering that metabolic alterations have been suggested as criteria for patient stratification [5], the concept of “glutamine addiction” has been revisited and it is clear that reliable in vivo systems are strongly needed. In turn, cellular metabolism of cancer has been dramatically changing. It is now accepted that metabolites like lactate and ammonia are not only by-products of metabolism with limited biological functions, but rather important contributors for cancer cells growth. More specifically, lactate was recently suggested to bridge glycolysis with mitochondria feeding the TCA cycle [6]. Remarkably, ammonia seems to account for more than 20% of the glutamine synthesis in breast cancer cells [7].

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