MAPK8 and neoplasm: This extremely high tumor specificity is derived from the following properties: IC3-PA needs the simultaneous presence of two distinct tumor-associated proteases, MMPs and uPA, for activation; it also requires binding to the CMG2 receptor which is expressed at high levels on tumor tissues; further, the novel effector moiety LF-W271A can specifically target the ERK pathway while sparing the WT LF's “off-target” proteolytic activity toward p38 and JNK pathways.