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A cancer drug can be used to treat patients with drug-resistant leukaemia, scientists have found.
The drug, axitinib, by Pfizer can act as a potent inhibitor of the dominant mutation that confers drug resistance to all well tolerated treatments in patients with certain types of leukemia, researchers said.
Researchers at the Institute for Molecular Medicine Finland FIMM and Faculty of Medicine, University of Helsinki and the Helsinki University Central Hospital Comprehensive Cancer Centre, in close collaboration with researchers at Pfizer, studied cancer cells from patients with chronic myelogenous and acute lymphoblastic leukemia (CML and ALL) that had developed resistance to currently available treatments.
These cancers are driven by the BCR-ABL1 fusion protein, and resistance to treatment developed due to a new genetic mutation in the BCR-ABL1 fusion gene in the cancer cells.
Researchers found that axitinib, a tyrosine kinase inhibitor currently approved to treat certain patients with advanced renal cell carcinoma, effectively eliminated these patient-derived drug resistant leukemia cells.
The researchers also defined the mechanism by which axitinib binds to the drug resistant version of the BCR-ABL1 protein, providing fundamental new molecular insights into how cancer causing kinases can be blocked.
“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said Brion Murray, Pfizer Research Fellow and one of the lead authors of the study.
“In the case of axitinib, it acts as two distinct keys - one for renal cell carcinoma and one for leukaemia,” Murray said.
“Since axitinib is already used to treat cancer, its safety is known and a formal exploration of its clinical utility in drug resistant leukaemia can now be done in a fast-track mode,” said Kimmo Porkka, Head of Haematology at Helsinki University Central Hospital Comprehensive Cancer Centre and one of the lead authors.
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