Targeting amino acid metabolism in cancer

Abstract

Metabolic rewiring is a characteristic hallmark of cancer cells. This phenomenon sustains uncontrolled proliferation and resistance to apoptosis by increasing nutrients and energy supply. However, reprogramming comes together with vulnerabilities that can be used against tumor and can be applied in targeted therapy. In the last years, the genetic background of tumors has been identified thoroughly and new therapies targeting those mutations tested. Nevertheless, we propose that targeting the phenotype of cancer cells could be another way of treatment aiming to avoid drug resistance and non-responsiveness of cancer patients. Amino acid metabolism is part of the altered processes in cancer cells. Amino acids are building blocks and also sensors of signaling pathways regulating main biological processes. In this comprehensive review, we described four amino acids (asparagine, arginine, methionine, and cysteine) which have been actively investigated as potential targets for anti-tumor therapy. Asparagine depletion is successfully used for decades in the treatment of acute lymphoblastic leukemia and there is a strong implication to apply it to other types of tumors. Arginine auxotrophic tumors are great candidates for arginine-starvation therapy. Higher requirement for essential amino acids such as methionine and cysteine point out promising targetable weaknesses of cancer cells.

Keywords: Amino acid metabolism; Arginine; Asparagine; Cancer; Cysteine; Methionine; Targeted therapy.