A team of Czech and US scientists have discovered a new method to fight cancer by blocking the access of a key nutrient, in this case an amino acid called glutamine, to cancer cells. This stops the cells from growing and they eventually die. Thanks to the promising results they have received funding of 40 million dollars for further clinical development.
Scientists from the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences in Prague and John Hopkins University in Baltimore built on an earlier research on an anti-cancer drug cultivated from bacteria found in Peruvian soil. Called DON, the compound actually blocks the cellular use of the protein building block called glutamine.
Pavel Majer is one of the members of the research team:
“DON is a natural compound that has been found in soil bacteria somewhere in Peru in the 1950s. The potential of the compound was realised right away.
“The compound entered the first clinical trials three years after the discovery but was found to be too toxic to be used. The tumours were receding but there were complications, mainly with the gastrointestinal tract.”
Several years ago, the John Hopkins University in Baltimore approached their colleagues from the Institute of Organic Chemistry and Biochemistry with the idea to renew the research, making the compound less toxic.
The researchers were looking for derivatives that release DON, creating a so-called prodrug, a compound that is not active as a drug but is converted in the body into the actual drug. Once it enters the body, it gets distributed differently than the drug itself.
They have also targeted certain enzymes that are overexpressed in cancer cells, driving the cancer cells to actually release DON. So how exactly does the compound work once it enters the body? Pavel Majer again:
“DON is called a ‘suicide substrate’. When the enzyme makes the mistake and takes DON instead of glutamine, the DON explodes like a hidden charge and kills the enzyme, binding it irreversibly. The cancer cells, without having those enzymes, cannot divide any longer and eventually die.
“So we were able to create compounds that are successful this way. They are differently distributed, they bypass the gastrointestinal tract, they are less toxic and they release this hidden charge in cancer cells.”
The clinical testing of the new drug application can start as soon as it is approved by the US Food and Drug Administration, which is expected to take from 15 to 18 months. The clinical trial on humans is likely to last for five to eight years and only then can the new drug be introduced to the market.
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