More and more medicines are becoming available that target a tumour’s specific traits. The use of chemotherapy is continually undergoing improvement.
Chemotherapy is still a widely used treatment for cancer. The substances used in this technique are targeted at rapidly dividing cells and thus affect not only tumour cells, but also cells in the intestines and hair follicles, causing diarrhoea and hair loss. ‘Now more and more medicines are coming available that specifically inhibit a molecule that the tumour depends on for growth. Which molecule that is can vary and depends on the mutations that have taken place in a cell,’ says professor of Clinical Pharmacy Henk Jan Guchelaar. A treatment using this sort of medicine is known as targeted therapy.
Professor of Medical Oncology Hans Gelderblom is one of the chief investigators in the DRUP study, in which patients with advanced or metastasised cancer are treated based on the tumour’s specific traits. ‘In this study we are investigating whether medicines that have already been approved for a certain type of tumour are also effective on other types of tumours. What is difficult is that a tumour is usually made up of cells with different traits, whereas a targeted medicine is only effective against one single trait. As a result of the so-called heterogeneous nature of the tumour, a proportion of the tumour cells do not respond to a particular medication and the tumour can continue to grow. This means that in the future more patients will receive combination therapies where multiple drugs are used simultaneously to target all the tumour cells,’ says Gelderblom.
Chemotherapy also continues to be used to fight cancer, but with fewer and fewer harmful side effects. ‘We are trying to improve existing chemotherapy by making minor changes to the substances used,’ says researcher and professor Sjaak Neefjes. Doxorubicine, for example, works well against cancer cells, but is also harmful to the heart. ‘We are trying to better understand what causes that side effect and are looking to see if we can modify the substance in such a way that it will still work against cancer, but produce fewer side effects,’ according to Neefjes.
Another problem with chemotherapy is that with a portion of the patients, certain substances don’t break down well. Guchelaar explains, ‘Since 2013 we have been giving a preliminary test to patients who will be receiving chemotherapy with fluoropyrimidines. If they aren’t good at breaking down substances such as 5-fluorouracil or capecitabine, we give them a reduced dosage. With this specially tailored chemotherapy we can now prevent half of the side effects. We continue to do research into better tests so we can spare even more people the sometimes serious side effects.’
For the development of targeted medicines, Leiden offers unique possibilities. ‘Here we’ve got researchers who can find proteins, chemists who can synthesise substances, a top-notch Good Manufacturing Practice (GMP) facility at LUMC for producing medications and the Centre for Human Drug Research (CHDR), which can test substances on test subjects,’ as Neefjes summarises it. ‘All these partners allow the development of a drug development board that can assist researchers who have an idea for a new drug.’ This makes Leiden the place where the next step can be taken in cancer drug development.
European Lead Factory research project (medicinal chemistry)