Scientists from the Institute of Cancer Research have warned against drugs specifically aimed at two key cancer targets.
The two targets are CDK8 and CDK19 – molecules implicated in the development of bowel and specific blood cancers which are touted as possible future drug targets for other types of cancer, inflammatory, cardiovascular and viral diseases.
Researchers at the ICR found that drugs specific to each respective target produced adverse side effects too severe for animal models when delivered in doses high enough to exhibit anti-cancer activity.
An initial study found the drugs to have potent anti-cancer effects when tested in lab-grown cell lines.
However, when tested in mouse models of both bowel and blood cancer, the CD8/19 drugs led to underwhelming anti-cancer activity as well as serious side effects in gut and bone tissue, negative effects on the immune system, and negative affects on stem cells when delivered continuously.
As a result, researchers concluded that the drugs should either cease to be progressed in humans or be used with extreme caution in trial conditions, regardless of their potent anti-cancer activity.
“To innovate in cancer treatment, we need to discover completely new class of drugs that target the 500 or so known cancer-causing genes that haven’t yet been exploited,” said study co-leader Professor Paul Workman, Chief Executive of the ICR. “Targeting these less explored cancer genes is potentially very high reward, but also high risk because we are hitting molecules in cancer cells that have never been targeted before.
“While we definitely can’t rule out that situations might be found in which targeting CDK8/19 might be useful in particular cancers or other diseases, we do feel that it’s prudent to warn that if such treatments are progressed to the clinic then this should be done with extreme caution because of the potential side-effects.”
“While these concerns about adverse side-effects and modest anti-cancer effects of CDK8/19 drugs are clearly disappointing, our work sheds critical new light on how CDK8 and CDK19 function in both normal and cancer cells.
“Scientists can also use our prototype drugs to continue to study the role of CDK8/19 in health and disease and potentially to discover currently unforseen medical uses.”