Ninety years ago, Warburg discovered that many animal and human tumors have high affinity for glucose, breaking down large amounts of glucose into lactic acid. He also pointed out that cancer is caused by metabolic changes and loss of mitochondrial function.
In addition to the key role of glucose, glutamine plays an important role in the growth of cancer cells. These arbitrary views have been replaced and perfected in the past decades.
The multipotency of glutamine powder in cell functions, such as energy synthesis, macromolecule synthesis, mTOR activation and reactive oxygen species balance.
Tumor cells overactivate renal glutaminase (GLS), while normal cells catalyze glutamine metabolism by hepatic glutaminase (GLS2). It is possible to selectively develop GLS inhibitors in clinic.
Targeted inhibition of some carcinogenic genes makes cancer cells dependent on glutamine, so the combination of targeting inhibitors and glutamine metabolism plays a synthetic lethal role.
Because of the complexity of the pathogenesis of cancer and many uncertainties about the physiological mechanism of glutamine in human body, for example, in 13 years, Professor Shi Yigong of Tsinghua University pointed out that the main role of glutamine metabolism is to produce amines for antagonizing the acidic environment of cancer. Therefore, the combination of GLS inhibitors and other targets has become the trend of development.
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