Metabolic Reprogramming of Cancer by Chemicals that Target Glutaminase Isoenzymes

Area of Science:

• Oncology
• Cancer Metabolism
• Biochemistry

Background:

• Tumor metabolic reprogramming is a hallmark of cancer, with altered glutaminolysis being a key feature.
• Glutaminase (GLS) enzymes regulate the initial step of glutamine metabolism, and their expression correlates with cancer malignancy and growth.
• GLS has oncogenic properties, while GLS2 acts as a tumor suppressor.

Purpose of the Study:

• To review metabolic pathways rewired in cancer.
• To elucidate the roles of glutaminase isoforms in cancer.
• To identify metabolic circuits regulated by glutaminases and anticancer drugs targeting them.

Main Methods:

• Literature review focusing on glutaminase connections with oncogenes and tumor suppressor genes.
• Analysis of strategies targeting glutaminase isoenzymes to deactivate cancer metabolism rewiring.
• Compilation of metabolic enzymes, transcription factors, signaling pathways, and chemical inhibitors related to glutaminase.

Main Results:

• Glutaminase isoenzymes are linked to key oncogenes and tumor suppressor genes.
• Specific inhibitors for GLS and GLS2 isoforms have been identified.
• These inhibitors demonstrate synergistic and therapeutic potential in various tumor types.

Conclusions:

• Glutaminase isoforms play critical roles in cancer metabolic rewiring.
• Targeting glutaminase isoenzymes with specific inhibitors offers a promising therapeutic strategy for multiple cancers.
• This review highlights metabolic pathways, glutaminase roles, and the therapeutic potential of glutaminase inhibitors.