Abstract 2499: Single agent activity of checkpoint kinase inhibitor PF-477736, in a MYC-driven lymphoma model

Abstract

Abstract CHK1 and CHK2 are protein kinases that function as effectors of cell cycle checkpoint arrest following DNA damage. Small molecule inhibitors with specificity for CHK1 such as PF-477736 (Blasina et al, 2008 Mol Cancer Ther 7:2394) and others with specificity for CHK1 and CHK2, are currently in phase 1 clinical evaluation in combination with chemotherapeutic agents known to induce DNA damage. We therefore hypothesized that inhibitors of CHK1/CHK2 may have single agent activity in tumours with oncogene-induced DNA damage. Cell lines derived from Eμ-MYC driven murine lymphomas display intrinsic DNA damage detected by γH2AX foci staining. Within 2 hours of 5..