Menezes dos Reis, L. et. al.

Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells

Menezes dos Reis, L. et. al. J Biol Chem. 2019 April 30.
doi: 10.1074/jbc.RA119.008180

TNBC tends to have a worse prognosis than hormone receptor and/or HER-2 positive breast cancer, in part because TNBC has no known treatment targets. Many investigators are studying this disease to find molecular characteristics that can be used for therapies.

The investigators noted that TNBC commonly uses glutamine, an amino acid, to multiply and survive. They began their study by blocking TNBC cells from using glutamine by exposing them to the drug known as Telaglenastat, or CB-839. CB-839 blocks the cellular enzyme that allows glutamine to be broken down and used for fuel. As expected, some TNBC cells survived despite this blockade, indicating that some cases of TNBC use other pathways besides glutamine metabolism to survive.

The TNBC cells that were resistant to CB-839 were studied further. Two enzymes that metabolize fatty acids, CPT1 and CPT2, were elevated in the cells. The team then took these cells and blocked the activity of CPT1 in addition to exposing them to CB-839. They found that this dual treatment slowed down the growth and migration of TNBC cells significantly. In fact, the cells were more effectively halted than when exposed to CPT1 blockade or CB-839 treatment alone.

This study helps to clarify how TNBC survives by identifying new biologic features within the cells. Moreover, it has provided a possible new treatment modality for the disease. It is expected that further research will be conducted to determine if these findings can ever be safely applied to humans.