ABSTRACT
Glutamine, as a conditionally essential amino acid of many kinds of tumors, has a great influence on the occurrence and development of tumors. In recent years, the research on glutamine metabolism has made rapid progress, and many related drugs have been in preclinical and clinical research. Glutamine is involved in energy generation, redox balance, macromolecular synthesis and signal transmission in tumor cells. Transporters and metabolic enzymes of glutamine are potential targets for tumor treatment. This paper reviews the anti-tumor drugs based on glutamine metabolism and provides guidance for the development of new drugs.
ABSTRACT
Tumor cells use several metabolic pathways to support bioenergetic and biosynthetic demands of proliferation. In addition to glucose, glutamine is an important source of precursor substances and energy for cancer cell growth. Glutaminase (GSL) activity is associated with Ras, c-Myc, and other oncogenes, as well as Rho GTP enzyme. Many preclinical studies have confirmed that glutamin-ase inhibitors not only exhibit anti-tumor activity, but can also remarkably enhance the sensitivity of resistant cancer cells to targeted drugs. At present, the novel GSL inhibitor CB-839 has entered phase I clinical trials and is expected to become a new drug for cancer treatment. This paper reviews the research progress on this novel glutaminase inhibitor and its antitumor activity.