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Gene Signature Diagnostic to Measure LKB1 Loss and MEK Inhibitor Sensitivity
Description of Technology
A Vanderbilt research group has discovered a diagnostic to identify patients with non-small cell lung cancer that would respond to MEK inhibitor therapies. This diagnostic indirectly measures loss of tumor suppressor activity by the protein LKB1. One approach to determine MEK inhibitor sensitivity, which is measurement of LKB1 mutations, misses 50% of patients who would benefit from these drugs. This diagnostic measures expression of a small panel of genes to identify a larger population that is sensitive to MEK inhibition.
Validated in human-derived non-small cell lung cancers:
Mouse models of LKB1 loss of function diverge from human models.
Doubles detection of MEK inhibitor-sensitive patients:
Functional loss of LKB1 is two times more likely than a LKB1 gene mutation.
Adds an additional dimension to a patient stratification strategy:
LKB1 functional loss independently predicts drug sensitivity. It is complementary to, but independent of, well-characterized mutations such as RAS and RAF.
Inventors:David CarboneJacob Kaufman