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Editor's Corner

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The cover presents H&E staining of a 10 mm sectioned MCF7 mammary carcinoma tumor at 60x magnification, isolated thirty days after cessation of a two day combined exposure to the MEK1/2 inhibitor PD184352 and the Chk1 inhibitor UCN-01. Similar data were also obtained in an estrogen independent mammary carcinoma cell line, MDA-MB-231. In the manuscript by Hawkins et al. UCN-01 is shown in vitro and in vivo to promote activation of ERK1/2 which can be blocked by inhibitors of MEK1/2. Inhibition of MEK1/2 synergized with UCN-01 exposure to specifically promote tumor cell death, whilst being apparently non-toxic to animals or to non-transformed cells in vitro. Studies by several groups have argued that simultaneous inhibition of two mutually complementary survival signaling pathways can result in tumor cell death. This grouping of signaling modulators thus appears to be a promising combination regimen that certainly merits further testing.