CARESS · A new methodology based on an advanced molecular probe for early detection of DPD enzyme deficiency in oncological patients, also enabling a personalised and effective drug management""

Amongst all the chemotherapy agents, 5-FU (fluorouracil) is being in use since 40 years, and is one of the most successful and widely employed in the treatment for breast, colon, and skin cancer, three of the most frequently occurring malignant tumours. In general, 5-FU is relatively well tolerated at standard doses, but there are some important issues that must be duly taken into consideration: 1)Around 8% of patients manifest a genetic variation that leads to a deficiency of an enzyme called Dihydropyrimidine dehydrogenase (DPD) that is crucial for the metabolism and deactivation of 5-FU. This causes several toxic reactions like mucositis, diarrhea, neutropenia, cerebellar ataxia, cerebellar dysfunction, and can even be fatal at the very first dose of 5-FU, with a mortality rate of about 0,5%. About 30% of patients suffer from severe toxicity effects after being treated with 5FU. Despite many approaches have been proposed for DPD deficiency screening, none of the current strategies are adequate to mandate routine DPD testing prior to starting a 5-FU based therapy. The CARESS project proposes to implement the first, compact, cheap, accurate and standard system for measuring the DPD activity level, thus allowing for fast screening of DPD deficiency and for real time adjusting the therapy administered to the patient through a pharmacokinetic approach, allowing to maximise the therapeutic efficacy, abating the costs associated to the management of the therapy and, most importantly, to limit the dangerous side effects for the patients. The system will take as input a small blood sample and will rely on the chemical interaction between a 5-FU analogous chemical probe with the sample, which will release in the solution ions that can be easily detected and measured through optical analysis.""