Acute lymphoblastic leukemia is one of the cancer types for which MELK-inhibitors are being tested.WIKIMEDIA, JAMES GRELLIERA protein thought to be essential for cancer cells may not be so essential after all, according to a study published today (March 24) in eLife. Researchers at Cold Spring Harbor Laboratory (CSHL) in New York used CRISPR-Cas9 to knock out the gene for maternal embryonic leucine zipper kinase (MELK), finding no effect on cancer cell proliferation. The result contradicts the conclusions of previous studies regarding the protein’s role, and suggests that MELK-inhibiting drugs—currently in preclinical and clinical development—may be killing cancer cells via off-target mechanisms.
“From the literature, there’s a lot of evidence that this is a very suitable therapeutic target,” said Mathieu Bollen, a cancer researcher at the University of Leuven, Belgium, who was not involved in the study. “What they show here is that the fitness of cancer cells is not affected by removal of the kinase. . . and in fact that the current clinical trials as they’re conceived now are based upon the wrong assumptions.”
First identified in the late 1990s, MELK has been linked to various biological processes, from programmed cell death to neurogenesis. Levels of MELK are often abnormally high in tumor cells, and multiple studies have reported that blocking production of the protein using RNA interference (RNAi) can halt cell proliferation in several ...
