Periodic Reporting for period 1 - TARGETOF (Mass cytometry nanotools for intracellular target engagement. Towards precision medicine.)
Période du rapport: 2021-09-01 au 2023-08-31
• What is the problem/issue being addressed?
Cancer is the second highest cause of death in Europe, with 3.7 million estimated new cases and 1.9 million deaths each year. One of the main strategies in recent cancer therapy has been the development of drugs which target multiple cellular proteins at the same time. This strategy aims to block simultaneously different cancer pathways and thus it is expected to avoid the resistance to therapy. The drawback of this strategy is the appearance of side effects which may force a reduction in the dose. Then, it is clear that a better understanding of the targets of a drug is the key for a personalized cancer therapy, since most effective drugs with reduced side effects could be individually selected. This project tries to develop of novel methods based on nanotechnology to detect multiple targets in a single experiment and, in doing so, help fighting cancer.
• Why is it important for society?
The project has developed new tools to better understand cancer disease in a personalized manner, using the new technology of mass cytometry. These tools can contribute to patient´s health by improving diagnostics and prediction of disease outcomes, while informing medical doctors of the sensibility of each patient to a given treatment in a personalized manner. The technology can also help scientist understand the mode-of-action of drugs and why they produce side effects. Early understanding of the disease in a personalized manner means prevention, and prevention means a better management of disease, with more rapid and efficient treatment.
• What are the overall objectives?
The central aim of this research project is to develop a novel method based on nanotechnology and the new technique of mass cytometry to capture the targets of a drug for further analysis. The project objectives are: to synthesise nanoparticles detectable by mass cytometry, to develop a novel assay for mass cytometry analysis and to validate the assay by comparison with conventional methods.
Cancer is the second highest cause of death in Europe, with 3.7 million estimated new cases and 1.9 million deaths each year. One of the main strategies in recent cancer therapy has been the development of drugs which target multiple cellular proteins at the same time. This strategy aims to block simultaneously different cancer pathways and thus it is expected to avoid the resistance to therapy. The drawback of this strategy is the appearance of side effects which may force a reduction in the dose. Then, it is clear that a better understanding of the targets of a drug is the key for a personalized cancer therapy, since most effective drugs with reduced side effects could be individually selected. This project tries to develop of novel methods based on nanotechnology to detect multiple targets in a single experiment and, in doing so, help fighting cancer.
• Why is it important for society?
The project has developed new tools to better understand cancer disease in a personalized manner, using the new technology of mass cytometry. These tools can contribute to patient´s health by improving diagnostics and prediction of disease outcomes, while informing medical doctors of the sensibility of each patient to a given treatment in a personalized manner. The technology can also help scientist understand the mode-of-action of drugs and why they produce side effects. Early understanding of the disease in a personalized manner means prevention, and prevention means a better management of disease, with more rapid and efficient treatment.
• What are the overall objectives?
The central aim of this research project is to develop a novel method based on nanotechnology and the new technique of mass cytometry to capture the targets of a drug for further analysis. The project objectives are: to synthesise nanoparticles detectable by mass cytometry, to develop a novel assay for mass cytometry analysis and to validate the assay by comparison with conventional methods.
This project allowed the development of a toolkit based on nanotechnology for the new technique of mass cytometry. It has developed nanoparticles, antibodies, methods and protocols for this technique with broad applications in cancer research. Being disseminated through conferences of different disciplines, these tools have garnered the attention of clinicians interested in using such devices for their respective specialties. The results of this project opened the avenue to develop further tools for disease diagnosis in future projects in collaboration with the Health System.
Being one of the most challenging steps in drug discovery, the isolation and detection of targets has not been previously explored by means of mass cytometry. Since this equipment became commercially available in 2014, the opportunities to develop new assays are huge at the moment. Mass cytometry adds to the current available techniques a unique feature, the possibility to run dozens of markers simultaneously. By developing novel nanotools for mass cytometry with application in the biomedical sector, this project aimed to impact the diagnostic capabilities of current techniques. The use of such nanotools in future studies with patient samples has the potential to approach precision medicine, by interrogating cells from patient biopsies with a battery of drugs before treatment decision. The versatility of the chemical approach has as well the potential to be applied to different diseases and detection techniques, opening a wide area for future collaborative research at the European level. The devices also have the potential to provide essential mechanistic information about the drug to facilitate subsequent translational efforts, e.g. the identification of the patient population that would benefit the most of the selected treatment. Once established as a routinary technique in National Health Systems the nanodevices have the potential to provide with important information which will help medical doctors to reach accurate decisions, reducing the disease burden and aiding to understand and fight one of the most challenging medical problems in Europe.