Multiple DNA damage-dependent and DNA damage-independent stress responses define the outcome of ATR/Chk1 targeting in medulloblastoma cells

Targeting of oncogene-driven replicative stress as therapeutic option for high-risk medullobastoma was assessed using a panel of medulloblastoma cells differing in their c-Myc expression [i.e. group SHH (c-Myc low) vs. group 3 (c-Myc high)]. High c-Myc levels were associated with hypersensitivity to pharmacological Chk1 and ATR inhibition but not to CDK inhibition nor to conventional (genotoxic) anticancer therapeutics. The enhanced sensitivity of group 3 medulloblastoma cells to Chk1 inhibitors likely results from enhanced damage to intracellular organelles, elevated replicative stress and DNA damage and activation of apoptosis/necrosis.

Source: Cancer Letters - May 10, 2018 Category: Cancer & Oncology Authors: Katharina Kr üger, Katharina Geist, Fabian Stuhldreier, Lena Schumacher, Lena Blümel, Marc Remke, Sebastian Wesselborg, Björn Stork, Nicolaj Klöcker, Stefanie Bormann, Wynand P. Roos, Sebastian Honnen, Gerhard Fritz Tags: Original Articles Source Type: research