Antique anti-coagulants may hold the key to a new lung cancer treatment

Image: Producing man-made molecules based on natural extracts, such as biscoumarin, has uncovered potential future treatments for lung cancer. (Photo courtesy of Hey Paul Studios [cc by 2.0], via Flickr) By James Bowers PhD | SciComm Officer, TV Researcher, Science Presenter and Science Journalist

Genetic variations in patients can render lung cancer medicines ineffective. Prof. Marc Diederich and his colleagues ascertained a biscoumarin-derivative to target patients that are resistant to other treatments.

Lung cancer is the most common cancer in the world and, with such a crucial role of this organ in the human body, it’s easy to understand the importance of finding an effective cure. Current research into finding new treatments aims at seeking molecules that can attack specific cancer cells. However, not every patient or cancer are the same due to genetic variation and this means that we are unlikely to find a one-size-fits-all medicine. A simple difference in the genetic code can make cancer cells resistant to treatments.

Dicoumarol: a long history

Prof. Diederich’s team focus a lot of their research on finding new cures to target specific cancer cells that are normally resistant to other therapies. They focus on developing derivatives of natural molecules and their most recent trial used a re-synthesized version of the molecule biscoumarin; a derivative of dicoumarol. 

Dicoumarol, an anti-coagulant like warfarin, has quite unique origins being first discovered 1939 by Dr. Karl Paul Link. A decade earlier, in the 1920s, Dr. Link laid his hands on some blood samples collected from cows during an epidemic in the US and Canada. Lots of cattle at the time were dropping dead in the masses due to blood loss through hemorrhaging. It was later discovered that the clovers and hay the cows were eating had gone rotten.

As it turns out the fungus rotting the hay was also responsible for a significant chemical change in the food supply. The fungus growing on the clover converted coumarin, which is produced naturally by the plants, into dicoumarol. After the cows ate the hay, the dicoumarol entered their bloodstream where it acted as a very powerful anti-coagulant, leading to death by uncontrollable bleeding. It sounds quite distasteful but from this discovery, anti-coagulants such as warfarin were developed and used as medicines.

Dicoumarol derivatives: anticoagulants as innovative lung cancer cures?

Now, in 2018, Prof. Diederich and his team have published results using molecules derived from the same origin.  Their paper in Cancer Letters, shows how a modified and re-synthesized version of biscoumarin obtained from the lab of Prof. Artur Silva (University of Aveiro, Portugal) can destroy lung cancer cells and synergize with last generation targeted anticancer drugs, the so called BH3 mimetics. It even worked in cells that are resistant to other treatments and so could provide a new drug molecule to treat lung cancer – particularly in patients where other molecules are ineffective.  

 

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