Arginine deprivation as a treatment approach targeting cancer cell metabolism and survival: A review of the literature

Abstract

Amino acid requirement of metabolically active cells is a key element in cellular survival. Of note, cancer cells were shown to have an abnormal metabolism and high-energy requirements including the high amino acid requirement needed for growth factor synthesis. Thus, amino acid deprivation is considered a novel approach to inhibit cancer cell proliferation and offer potential treatment prospects. Accordingly, arginine was proven to play a significant role in cancer cell metabolism and therapy. Arginine depletion induced cell death in various types of cancer cells. Also, the various mechanisms of arginine deprivation, e.g., apoptosis and autophagy were summarized. Finally, the adaptive mechanisms of arginine were also investigated. Several malignant tumors had high amino acid metabolic requirements to accommodate their rapid growth. Antimetabolites that prevent the production of amino acids were also developed as anticancer therapies and are currently under clinical investigation. The aim of this review is to provide a concise literature on arginine metabolism and deprivation, its effects in different tumors, its different modes of action, as well as the related cancerous escape mechanisms.

Keywords: Apoptosis; Arginine depraving factors; Arginine deprivation; Autophagy; Cancer therapy; Escape mechanisms.