Selectively depleting the energy of cancer cells: A new therapeutic paradigm

Abstract

Over the past fifty years the somatic mutation theory of cancer has emerged as the most successful explanation of the molecular phenotype of human cancer cells. Normal non-mutated genes may, however, also play a role in carcinogenesis. In particular these may contribute to aerobic glycolysis and the potential interaction of PKM2 and Cdk4 in helping the nascent cancer cell avoid apoptosis by the interaction of their respective amino acid sequences: anionic SDPTEA and cationic PRGPRP. It is proposed that cancer first occurs in normal tissues cells which, as part of the premalignant phenotype have switched from PKM1 to PKM2 expression, and this phenotype persists as cancers age and further molecular biological mechanisms to avoid apoptosis and encourage aerobic glycolysis emerge. PRGPRP and several congeners have been shown to kill a wide range of in vitro cancers by necrosis by producing a fall in ATP without harming normal diploid cells. The ATP depletion is suggested to result from inhibition of aerobic glycolysis and has resulted in the first therapeutic agent that globally selectively kills cancer cells by depriving them of energy.