Tinkering with molecules can lead to better treatments for cancer patients, explains Floris Rutjes, professor of Organic Chemistry. Today’s cancer drugs often have severe side effects. Although they attack the tumours, they also attack healthy cells. “Ideally, cancer drugs should focus exclusively on the tumour cells,” says Rutjes. “And that can be done by binding them to antibodies that attach themselves only to tumour cells. This binding process also ‘cages’ the medicine. The drug is only released close to the tumour where it can it do its work in a targeted manner.” These antibody-drug conjugates (ADCs) are a promising trend in drug development. By building new molecules, Rutjes' research group is providing the essential first step. Manipulating medicines After a tampering with molecules in the lab for years, the BCN molecule was synthesised in 2010. It is highly reactive but only couples to specific other molecules and is relatively easy to make. By way of comparison: the first American version of such a ‘click-on’ molecule required twelve chemical steps. Rutjes' group synthesised BCN in four steps. “We found a simpler technology that also yielded a molecule with a faster reaction capacity.” BCN has been patented and is currently going into a clinical trial with cancer patients. The trial is taking place via Synaffix, a Radboud University spin-off founded by former associate professor Floris van Delft, in collaboration with pharmaceutical multinationals. In the meantime, Rutjes continues to work on a new technology that can modify medicines even better. With BCN, enzymes in the human body slowly decouple the drug, but he has now built another molecule, TCO, which decouples rapidly when an adjuvant is administered. In addition, TCO is much more reactive, which means that this technology can prove useful in visualising tumours with radioactive substances; those substances no longer have to circulate in the body for days with all the resulting side effects, but can be administered after circulation of the tumour-targeting antibody and click onto the antibody to visualize the targeted cells. TCO has also been patented. “If medicines are developed based on our technology, we want Radboud University to share in the revenue.” In addition, patents serve as quality assurance: “Without patents, pharmaceutical companies would never invest in new drugs.” Sometimes a molecule ends up somewhere completely different than expected. For example, at the request of the Dermatology Department of Radboud university medical center, Rutjes developed a molecule that inhibits certain enzymes in the skin tissue of psoriasis patients. These enzymes were thought to cause the skin inflammation. “That turned out not to be the case. Then the question is: can we do something else with these molecules?” That something else turned out to be malaria. The molecule formed the basis for a new malaria drug that will soon be clinically tested. “With our fundamental research, we are developing the molecular basis for medicines of the future.” Tip: Cherish trust in science “With new medicines and vaccines too. Don't be distracted by conspiracy theories and fake news.” Floris Rutjes (Heiloo, 1966) studied chemistry at the University of Amsterdam, where he also earned his PhD in 1993. He has been professor of Organic Chemistry at Radboud University since 1999. Photo: Dick van Aalst