Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with advanced hematologic malignancies.
Patients will receive CB-839 capsules orally two or three times daily. The study will be conducted in 2 parts. Part 1 is a dose escalation study to identify the recommended Phase 2 dose and will enroll patients with advanced and/or treatment-refractory Non-Hodgkin’s Lymphoma (NHL), Multiple Myeloma (MM), or Waldenström’s macroglobulinemia (WM)
In Part 2, all patients will receive the recommended Phase 2 dose. This part will enroll patients with advanced and/or treatment-refractory Non-Hodgkin’s Lymphoma (NHL), Multiple Myeloma (MM),
Glutamine – this can be used by cancer cells much like Glucose!
What is Glutamate?
Glutamate (from Glutamine) is one of your primary excitatory neurotransmitters. It has many important roles like stimulating your brain cells so you can talk, think, process information, learn new information, pay attention, and store information in short and long term memory.
Although glutamate is one of the most abundant neurotransmitters found in the brain, it exists in very small concentrations. Glutamate becomes an excitotoxin when it is in excess; meaning it overstimulates brain cells and nerves and results in neurological inflammation and cell death.
An excess of glutamate is a primary contributing factor to a wide variety of neurological disorders like autism, ALS, Parkinson’s schizophrenia, migraines, restless leg syndrome, tourettes, pandas, fibromyalgia, multiple sclerosis, Huntington’s chorea, and seizures.
Mercury in the body becomes more toxic in the presence of high levels of glutamate.
Excess glutamate also makes cancer cells proliferate and increases tumor growth and survival.
Additionally, glutamate receptors also pull in other excitatory substances into the cell besides glutamate, including all of the following:
• Aspartate (can also be converted into glutamate)
• Aspartic acid
• Glutamic acid
• Monosodium glutamate (MSG)
• Cysteine (But not n-acetyl-cysteine. However, does contain sulfur and too much sulfur can be counterproductive as well, so should be used mindfully.)