The value of this methodology was recently exemplified by the devalidation of the proposed oncoprotein maternal embryonic leucine zipper kinase (MELK): thus CRISPR-Cas9 deletion of MELK was tolerated in a range of cancer cell lines, and the clinical candidate MELK inhibitor OTS167 retained activity in MELK-knockout lines, indicating that the antiproliferative activity of this drug is mediated via an off-target mechanism (Lin et al., 2017). Here, MELK is linked to cancer.