The therapeutic effects of the blockbuster leukemia drug imatinib may be enhanced when given along with a drug that inhibits a cell process called autophagy, researchers from the Kimmel Cancer Center at Jefferson reported in the Journal of Clinical Investigation.
The cell-death effect of imatinib (Gleevec) was potentiated when chloroquine, an autophagy inhibitor, was given with imatinib for the in vitro treatment of chronic myeloid leukemia (CML) cells including the CML stem cells, according to Bruno Calabretta, M.D., Ph.D., professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University.
Autophagy is a process that allows cells to adapt to environmental stresses, and enables drug-treated CML cells to escape cell death. Imatinib is a tyrosine kinase inhibitor that suppresses proliferation and induces death of the malignant cells that cause CML. However, additional effects of the drug have not been studied in detail, according to Dr. Calabretta.
In this study, Dr. Calabretta's team, along with Dr. Paolo Salomoni's team from the MRC Toxicology Unit at the University of Leicester in the United Kingdom, found that imatinib induces autophagy in CML stem cells that overexpress a protein called p210BCR/ABL. Stem cells that express this protein have been historically resistant to imatinib and also to second-generation tyrosine kinase inhibitors, including dasatinib, nilotinib and bosutinib.