A molecular process involved in the action of anti-leukemia drugs has been discovered at Université de Montréal’s Institute for Research in Immunology and Cancer (IRIC). While calling into question a central tenet of oncology, this discovery, published today in the journal Cancer Cell, also holds promise for the development of effective treatments in the near future.
Headed by Dr. Guy Sauvageau, principal investigator with IRIC’s Molecular Genetics of Stem Cells Research Unit, the IRIC study focused specifically on acute myeloid leukemia (AML), the most common type of leukemia in adults.
The drugs tested are not used specifically to treat leukemia, but rather are representative of the range of pharmaceutical treatments used to treat human diseases. Their effects were tested both on the cells of mice carrying the gene for acute myeloid leukemia and on human cells. A table comparing the effect of each drug on each AML subtype provided insight, through the genetic sequencing that revealed similarities in anomalies between the different types of AML, into why certain drugs act on certain AML subtypes and not on others.
Dr. Sauvageau and his team were able to determine that several of the molecules tested could have a complementary effect on various AML subtypes by acting in combination, leading to the potential for more effective treatments.
Mubritinib: A promising drug
One of these drugs—-Mubritinib—-a protein kinase inhibitor that regulates cellular metabolism and was originally developed for the treatment of breast cancer, showed particular promise. “We observed that Mubritinib had a therapeutic effect on certain subtypes of AML for which there are few effective treatments,” explained Sauvageau, adding that the drug showed no toxicity in mice and little toxicity in human cells.
Mubritinib was subsequently modified at the IRIC before being patented. A large pharmaceutical company acquired the license and signed an agreement with the IRIC to mobilize an army of researchers with the aim of accelerating clinical trials in AML.
Revisiting the Warburg effect
In studying the electrochemical process behind Mubritinib’s mode of action, Dr. Sauvageau’s team stumbled upon another, unexpected, discovery. They observed that Mubritinib causes the death of cancer cells in an AML subgroup by arresting oxidative phosphorylation (OXPHOS) of the tumor cell—i.e., its oxygenation.
This discovery adds clarification, and even a caveat, to what is known in biochemistry as the Warburg effect.
Sauvageau is optimistic going forward. He believes that a new drug based on this study could reach the market within the next two to three years.
—Intertnet
Dr. Sauvageau and his team were able to determine that several of the molecules tested could have a complementary effect on various AML subtypes by acting in combination, leading to the potential for more effective treatments.
Mubritinib: A promising drug
One of these drugs—-Mubritinib—-a protein kinase inhibitor that regulates cellular metabolism and was originally developed for the treatment of breast cancer, showed particular promise. “We observed that Mubritinib had a therapeutic effect on certain subtypes of AML for which there are few effective treatments,” explained Sauvageau, adding that the drug showed no toxicity in mice and little toxicity in human cells.
Mubritinib was subsequently modified at the IRIC before being patented. A large pharmaceutical company acquired the license and signed an agreement with the IRIC to mobilize an army of researchers with the aim of accelerating clinical trials in AML.
Revisiting the Warburg effect
In studying the electrochemical process behind Mubritinib’s mode of action, Dr. Sauvageau’s team stumbled upon another, unexpected, discovery. They observed that Mubritinib causes the death of cancer cells in an AML subgroup by arresting oxidative phosphorylation (OXPHOS) of the tumor cell—i.e., its oxygenation.
This discovery adds clarification, and even a caveat, to what is known in biochemistry as the Warburg effect.
Sauvageau is optimistic going forward. He believes that a new drug based on this study could reach the market within the next two to three years.
—Intertnet
