Study examines cutting off glutamine and fatty acids, two well-known cancer food sources that tumors use to grow and survive.
Investigators from the Brazilian Biosciences National Laboratory have developed a strategy for slowing the growth of triple-negative breast cancer (TNBC) that involves cutting cancerous cells off from vital food sources.
The study, published in the Journal of Biological Chemistry, focused on TNBC tumors, which often lack estrogen progesterone receptors and human epidermal growth factor receptor 2 proteins. These are present in other breast cancers and permit certain targeted therapies. Since these types of tumors vary in genetic makeup, it has been a difficult task to find new markers to guide treatment.
Therefore, the investigators looked to glutamine and fatty acids, 2 well-known cancer food sources that tumors use to grow and survive. Glutamine, in particular, is incredibly important to tumor growth since it offers energy, carbon, nitrogen, and antioxidant properties.
Investigators found that by starving the cells by blocking glutamine and fatty acid metabolism, cancer cell growth and migration slowed.
They used the drug known as telaglenastat (CB-839), which prevents the processing of glutamine by deactivating the enzyme glutaminase and is currently in clinical trials to treat TNBC and other tumor types.
According to the press release, the molecular pathways that process lipids in the resistant cells were dramatically altered, said Sandra Martha Gomes Dias, a cancer researcher at the Brazilian Biosciences National Laboratory. In particular, levels of the enzymes CPT1 and CPT2, which are critical for fatty acid metabolism, were increased.
"CPT1 and 2 act as gateways for the entrance of fatty acids into mitochondria, where they will be used as fuel for energy production," Dias said in the press release. "Our hypothesis was that closing this gateway by inhibiting CPT1 in combination with glutaminase inhibition would decrease growth and migration of CB-839-resistant TNBC cells."
According to Dias, the double inhibition slowed proliferation and migration in resistant TNBC cells more than individual inhibition of either CPT1 or glutaminase. These results provide new genetic markers to guide drug choices in patients with TNBC, the study authors concluded.