Interruption of the Ras/MEK/ERK signaling cascade enhances Chk1 inhibitor–induced DNA damage in vitro and in vivo in human multiple myeloma cells

Abstract excerpt

The role of the Ras/MEK/ERK pathway was examined in relation to DNA damage in human multiple myeloma (MM) cells exposed to Chk1 inhibitors in vitro and in vivo. Exposure of various MM cells to marginally toxic concentrations of the Chk1 inhibitors UCN-01 or Chk1i modestly induced DNA damage, accompanied by Ras and ERK1/2 activation. Interruption of these events by pharmacologic (eg, the farnesyltransferase...

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