[HTML][HTML] Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors
A Thomas, CE Redon, L Sciuto… - Journal of Clinical …, 2018 - ncbi.nlm.nih.gov
Journal of Clinical Oncology, 2018•ncbi.nlm.nih.gov
Purpose Our preclinical work identified depletion of ATR as a top candidate for
topoisomerase 1 (TOP1) inhibitor synthetic lethality and showed that ATR inhibition
sensitizes tumors to TOP1 inhibitors. We hypothesized that a combination of selective ATR
inhibitor M6620 (previously VX-970) and topotecan, a selective TOP1 inhibitor, would be
tolerable and active, particularly in tumors with high replicative stress.
topoisomerase 1 (TOP1) inhibitor synthetic lethality and showed that ATR inhibition
sensitizes tumors to TOP1 inhibitors. We hypothesized that a combination of selective ATR
inhibitor M6620 (previously VX-970) and topotecan, a selective TOP1 inhibitor, would be
tolerable and active, particularly in tumors with high replicative stress.
Abstract
Purpose
Our preclinical work identified depletion of ATR as a top candidate for topoisomerase 1 (TOP1) inhibitor synthetic lethality and showed that ATR inhibition sensitizes tumors to TOP1 inhibitors. We hypothesized that a combination of selective ATR inhibitor M6620 (previously VX-970) and topotecan, a selective TOP1 inhibitor, would be tolerable and active, particularly in tumors with high replicative stress.
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