From researching the chemical effects of hundreds of drugs on cell signaling pathways, a team of researchers has discovered that axitinib – a drug approved for the treatment of kidney cancer – can also attack other types of cancer via a different route.
The study, led by researchers from the Department of Clinical Science at the University of Bergen in Norway, is published in the Proceedings of the National Academy of Sciences and there is a comment on the discovery of the “useful off-target effect” in the journal Science Signaling.
The discovery comes from a growing field of research called drug repurposing,which investigates whether drugs already approved to treat one disease or condition are effective and safe for treating other diseases.
The field is growing for a number of reasons. One is that it takes a lot of time, effort, and cost to develop a brand new drug, often more than 14 years. Drug repurposing can cut these significantly.
Many compounds approved for other uses have already been tested in humans, so detailed knowledge about their safety and how they affect the body at different doses is already available. This speeds up their journey to clinical use through clinical trials and review by drug regulators.
Another reason that drug repurposing is attracting more attention in drug development is because of increasing knowledge about how diseases arise and progress at the molecular level. This provides unprecedented opportunities for studying compounds that target molecular pathways – including those in drugs that are already approved for clinical use.
The researchers at the University of Bergen, led by Prof. Karl-Henning Kalland, have for many years been searching for compounds that block the chemical signals that drive the growth and spread of cancer cells.
Axitinib is approved for use as a “tyrosine kinase inhibitor” that blocks the triggering of angiogenesis – the generation of new blood vessels, which tumors rely on to grow.
The new study shows that axitinib has a useful off-target effect in that it also knocks out a type of “Wnt signaling” cell communication pathway that encourages cells to mutate.
As around 90 percent of all cancer arises from mutations in cells, the researchers believe axitinib could be effective against several forms of the disease, including breast, prostate, and colorectal cancers.
The team also discovered a handful of other promising candidates, which they are testing further and hope to report on soon.
The off-target effects – such as blocking signaling mechanisms – do not necessarily mean these compounds will be enough to treat the particular cancer, as Prof. Kalland explains:
“Knocking out these mechanisms will not cure cancer alone, but be a contribution in the fight against cancer. Cancer has to be defeated with a combined strategy.”
In the case of axitinib, Prof. Kalland believes the effect his group has discovered could be used in combination with immunotherapy.
Immunotherapy is a type of cancer treatment designed to boost the body’s natural defenses to fight the disease.
“It is a very interesting coincidence that the specific signaling pathway that is getting attacked, both leads to a blocking of the cancer cells and stimulates the activation of immune cells, creating a great synergy effect. This synergy is to be followed up.”
Prof. Karl-Henning Kalland