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Glucose Transporter Inhibition: Potential Treatment of Certain Lung Cancers

By: Julia Fiederlein
Posted: Tuesday, July 28, 2020

Boyi Gan, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues suggested that glucose transporter inhibitors may prove to be effective in the treatment of lung cancers with high expression of the amino acid transporter known as solute carrier family 7 member 11 (SLC7A11). The findings, which were published in Nature Cell Biology, may provide insight into treatments that could target the metabolic vulnerabilities of these lung cancer cells.

In brief, the SLC7A11 transporter is the main source of the amino acid cystine. Cells convert cystine into cysteine in a NADPH-dependent reaction, which aids in the buildup of glutathione. Consumption of NADPH is essential for cell redox homeostasis.

“SLC7A11 is frequently overexpressed in cancers and has a well-established role in maintaining glutathione levels which reduce cancer cell death,” stated Dr. Gan in an MD Anderson press release. “Cancer cells with high levels of SLC7A11 and a high demand for cystine become dependent on glucose for survival.”

The investigators conducted xenograft experiments using 4-to-6-week-old athymic nude mice, cell culture experiments, and several assays to identify a treatment option that targets this pathway. The results suggested that the reduction of cystine to cysteine is a crucial NADPH consumer in cancer cells highly expressing SLC7A11. The investigators proposed that glucose transporter inhibition would limit NADPH production, leading to disulfide accumulation, redox defects, and cell death. Most cells with high expression of SLC7A11 have BAP1 and KEAP1 mutations, which could potentially serve as biomarkers for kidney cancers that may benefit from glucose transporter inhibition. The investigators noted that this treatment may also be effective in renal cell cancers with high expression of SLC7A11.

Disclosure: For full disclosures of the study authors, visit nature.com.



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