Deciphering the Hallmarks of Cancer; Deregulation of Cellular Energetics

Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou & Meletios Dimopoulos, A.^*

Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece

Dr. Meletios Dimopoulos, A., Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece.

Keywords: Cancer; Hallmark; Metabolism; Immunotherapy

Abstract

In 2011, Hanahan and Weinberg presented the next generation of hallmarks of cancer, by providing an update of their initial review [1,2]. Deregulation of cellular energetics and evasion of immune destruction were proposed as emerging cancer hallmarks [2]. Currently, accumulating data support the reprogramming of energy metabolism as a cardinal event in carcinogenesis and sustainable cancer cell survival. Warburg was the first to describe the effect of metabolism reprogramming in cancer cells [3,4]. It was hypothesised that mitochondrial dysfunction in cancer cells resulted in a shift towards glycolysis, even in the presence of oxygen in the tumour microenvironment, the so-called “aerobic glycolysis”. Throughout the years, aerobic glycolysis among cancer cells has been repeatedly confirmed; however the underlying pathophysiological mechanisms do not coincide with Warburg’s beliefs [5]. It has to be noted, though, that Warburg provided the basis for investigating cancer metabolism and his contribution remains widely appreciated [6].
Cancer cells are no longer considered as carrying mitochondrial defects [5]. Mitochondrial function is being reprogrammed in favor of glycolysis in order to provide important glycolytic intermediates to biosynthetic pathways resulting in macromolecules production, which is vital for cancer cell survival and proliferation [7].

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