BIOMARKERS OF RESPONSE TO NAE INHIBITORS

摘要

Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

主权项

1. A method for identifying a cancer patient for treatment with a NEDD8-activating enzyme (NAE) inhibitor comprising:
a) measuring at least one characteristic of at least one marker associated with at least one marker gene in a patient sample comprising tumor cells, wherein the at least one characteristic is selected from the group consisting of size, sequence, composition and amount; b) identifying whether the at least one characteristic measured in step a) is informative for outcome upon treatment with the NAE inhibitor; and c) identifying the patient for treatment with the NAE inhibitor if the informative characteristic indicates that the tumor cells comprise at least one marker gene whose mutational status indicates a favorable outcome to NAE inhibition therapy,wherein the at least one marker gene is a tumor suppressor with a relationship to the activity of a cullin ring ligase and wherein the NAE inhibitor is ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3 -d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulphamate.