Research Team Finds TTK Inhibitor Kills Lung Cancer Cells and Tumors in Mice

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FREDERICK, Md. -- High levels of the enzyme tyrosine threonine kinase (TTK) in many types of cancer cells, including lung cancer, contribute to uncontrolled cell growth. A study published by Frederick National Laboratory Director Ethan Dmitrovsky, M.D. and his laboratory team demonstrated that a promising anti-TTK treatment that acts against many of those types of cancer cells also results in lung cancer cell death. 

The study also found the treatment suppresses growth of tumors in lung cancer-bearing mice. This work was part of a collaboration with Tak Mak, Ph.D. and his research team at the Princess Margaret Cancer Centre, University Health Network in Toronto, Canada.

The treatment, CFI-402257, has been shown to be potent against TTK in many types of cancer cells in the laboratory, and is being tested in a Phase 1 clinical trial for treatment of advanced solid tumors. But CFI-402257 had not been tested in lung cancer, the leading cause of cancer death.

Xi Liu, Ph.D. a key coauthor on this study said CFI-402257 caused chromosomal instability and cell death in lung cancer cell lines in the laboratory and in animal models. CFI-402257 had a therapeutic effect in all examined lung cancer cells. The paper was published recently in Molecular Cancer Therapeutics and was spotlighted on the cover of the journal.

While CFI-402257 acted against the lung cancer cells, the team discovered it also enhanced MAPK, a pathway of enzymes in the cell that promotes cancer cell survival, growth, metastasis, and drug resistance. To remedy that, researchers hypothesized that a treatment that interrupted MAPK would cooperate with CFI-402257. They found that doing so increased the anti-cancer effects of CFI-402257.

The Frederick National Laboratory team was eager to collaborate with Mak, as the partnership enables these scientists to see their work in the laboratory translate into the clinic. This is because the Princess Margaret Cancer Centre is conducting clinical trials with CFI-402257. The authors propose that future clinical trials should determine whether CFI-402257 alone or in combination with a treatment to block the MAPK pathway is more effective against human lung cancers.

“We are excited about these findings and will exploit the implications in our ongoing clinical trials,” Mak said.