AsianScientist (Nov. 26, 2013) – Australian researchers have successfully targeted a signaling pathway to kill blood cancer cells in adult and childhood leukemia.
In findings published in the journal Cell Reports, researchers from the University of Melbourne’s Peter MacCallum Cancer Center combined an existing blood cancer treatment with a novel drug to attack the cancer-causing activity of the JAK2 protein in two places, leading to long-term survival in laboratory models of aggressive leukemia.
While other research has looked at attacking leukemia which are driven by mutated JAK2 using standard chemotherapy, these have failed as the cancer cells can survive the scatter-gun assault, according to lead author Professor Ricky Johnstone, head of the Cancer Therapeutics Program.
“To date, standard treatments for leukemia driven by mutated forms of JAK2 have had only limited success before the aggressive relapse of disease,” said Johnstone. “In our study, we combined JAK2 inhibitors with a novel inhibitor to target a second component of the same signaling pathway – and found cancer cells could not survive this precise, double-barrel hit.”
The international research study, conducted in collaboration with researchers at St. Jude Children’s Research Hospital in Memphis and Memorial Sloan-Kettering Cancer Center in New York, among others, also revealed why the mutated JAK2 protein has remained an elusive target for cancer researchers, according to first author, Dr. Michaela Waibel.
“As well as driving the growth and proliferation of aggressive adult and childhood leukemia, we found mutated JAK2 is especially insidious because it also boosts the activity of pro-survival molecules to ensure the cancer cells persist and flourish,” said Waibel. “This explains why our double approach, inhibiting both JAK2 and the survival molecules using a combination of drugs, was crucial to overwhelm the survival capacity of these cancer cells.”
Johnstone added that while the research is still in its early stages, the availability of the novel inhibitors for clinical use makes the laboratory results exciting.
“One of the drugs we used in our work is already approved for the treatment of adults with other cancers, while the second is in clinical development, so we hope our combination regimen could be available for patients with JAK2-driven leukemia in a matter of years,” said he said.
The article can be found at: Johnstone R et al. (2013) Combined Targeting of JAK2 and Bcl-2/Bcl-xL to Cure Mutant JAK2-Driven Malignancies and Overcome Acquired Resistance to JAK2 Inhibitors.
——
Source: Peter MacCallum Cancer Center; Photo: euthman/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
