Cancer Research Lab

Cellular autophagy appears to be a mechanism that the tyrosine kinase inhibitor imatinib (Gleevec, Novartis) inhibits chronic myelogenous leukemia and may also inhibit other types of malignant cells, German researchers report in the March issue of Leukemia.

“Gleevec was considered as a targeted anticancer drug which is specific for only certain types of malignancies,” senior investigator Dr. Hermann M. Schaetzl said, “and which acts in stopping cancer growth. We describe a much broader effect of this compound which might be beneficial for all kind of tumors.”

In previous studies, Dr. Schaetzl, of the Technical University of Munich, and colleagues found that imatinib increases the cellular clearance of intracellular protein aggregates by targeting the abl pathway and upregulating lysosomal activity.

In the current study, the team found that imatinib also activates the cellular autophagy machinery in mammalian cells in a dose-dependent fashion. Moreover, they observe that this happened “in all cell lines tested,” which strongly suggests this is not cell-type or species specific, but a generalized effect.

Autophagy, the investigators add, is a degradation mechanism mainly involved in the recycling and turnover of cytoplasmic constituents.

Autophagy may promote death in certain cancer cells, and the researchers point out that “this feature is in accordance with the anticancer potential of imatinib and may strengthen its pro-apoptotic function.”

They suggest further study in cancers that do not use autophagy as a protective mechanism. Under these circumstances, the investigators conclude, “the application of imatinib in combination with other autophagy-inducing drugs might not only inhibit tumour progression but even promote tumour regression.”