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Technology

These inventors found that a primary predictor of response to glutaminase inhibition is expression of the cystine/glutamate antiporter SLC7A11 (also known as xCT). Cells that express high levels of SLC7A11 are exquisitely sensitive to glutaminase inhibition, while those with low levels of SLC7A11 fail to respond. Therefore, SLC7A11 provides a promising theranostic marker for identifying patients that will respond to glutaminase inhibition therapies. Additionally, these inventors demonstrated that increasing levels of SLC7A11 is sufficient to sensitize cancer cells to glutaminase inhibitors. Interestingly, increasing the level of the amino acid dimer cystine (or monomer cysteine) that cancer cells are exposed to can similarly sensitize cancer cells to glutaminase inhibition, as this is a substrate of SLC7A11. Therefore, sensitizing cancer to glutaminase inhibitors by providing exogenous cysteine or SLC7A11 shows exciting potential as a new cancer therapeutic strategy.