Keeping Tumors Out of the MAPK Fitness Zone.

<b/> Greatest fitness of tumor cell subclones in patients undergoing MAPK-targeting therapies requires just-right levels of MAPK pathway signaling. New therapeutic approaches induce tumor cell death by intensifying MAPK signaling induced by inhibitor withdrawal in combination with DNA damage, or prevent selection of resistant clones with a steep fitness barrier imposed by triple combination of BRAF, MEK, and ERK inhibitors. Cancer Discov; 8(1); 20-3. ©2018 AACRSee related article by Hong et al., p. 74. ©2018 American Association for Cancer Research.