A novel sensor for chemotherapy

Chemotherapy is a cancer treatment that relies on chemical substances to alleviate symptoms and reduce tumour burden. 5-fluorouracil (5-FU) is a chemotherapeutic drug that has been successfully used for over 40 years and works by inhibiting DNA synthesis or transcription. It is generally well-tolerated and it is effective on rapidly dividing cells such as cancer cells.

However, some patients develop a genetic variation that leads to a deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme that catalyses the metabolism and deactivation of 5-FU. This leads to a number of serious toxic reactions and can even prove fatal. Screening for DPD deficiency is thus of outmost importance before starting 5-FU–based therapy.

The scope of the EU-funded CARESS project is to develop an easy and affordable method for testing DPD activity. The idea is that measuring DPD levels could be utilised to adjust patient therapy thereby maximising therapeutic efficacy.

CARESS' system will detect DPD activity in a small human blood sample through its interaction with a probe that resembles 5-FU. The automated electronic device will contain an optical sensor for detecting the iodide ions released from the chemical reaction with the probe, and correlate it to DPD levels.

Following identification of users' chemical, biological, technical and technological requirements, the consortium has proceeded with device prototype development. Among the ongoing project activities is appropriate processing of the sample to isolate peripheral blood mononuclear cells. Optimisation of the reaction conditions and stoichiometry as well as standardisation of the chromogenic detection of the iodide ions is underway.

By using a molecular probe that resembles 5-FU to detect DPD activity, the CARESS project hopes to revolutionise chemotherapy treatment by providing a rapid response. This is a definite improvement to existing methods based on mass spectrometry. Most importantly, the CARESS device could be used to routinely monitor patients receiving 5-FU therapy in a clinical setting.