Description
Cancer treatment represents a crucial unmet need of current medicine. Particular emphasis is placed on targeted cancer therapies. The main goal of this project is to develop a novel targeted therapy against different types of cancers overexpressing FGFRs. Within the project we will propose a novel targeted therapy for effective treatment of tumors based on FGF2-conjugates. We will design, produce and characterize FGF2-conjugates which will be used to bring highly cytotoxic drug into cancer cells. The project will be a starting point towards future anti-cancer therapies. We propose a novel, alternative approach of targeted delivery of cytotoxic agent, which would be beneficial to cancer patients. Bilateral relations will be strengthened by effective communication concerning the results and research methods. All groups involved in the project will benefit from the exchange of practical laboratory knowledge, experimental methods, scientific experience and ideas.
Summary of project results
Cancer treatment represents a crucial unmet need of current medicine. Particular emphasis is placed on targeted cancer therapies based on drugs that block the growth and spread of cancer cells by interfering with specific macromolecules, which are deregulated and play important role in tumor progression. The main goal of our project was to develop a novel targeted therapy against different types of cancers overexpressing fibroblast growth factor receptors (FGFRs). We proposed a novel approach based on the FGF2 molecule fused to a highly efficient cytotoxic drug to establish a delivery technique for effective killing of cancer cells. Our strategy is similar to construction of antibody drug conjugates (ADCs), which are showing clinical efficacy in cancer treatment. However, instead of antibodies we used the engineered growth factor as a delivery molecule specifically directing cytotoxic drug to cancer cell by binding to FGF receptors. Within the project we produced and thoroughly characterized FGF2 mutants suitable for coupling with cytotoxic agent. Using different conjugation strategies we obtained several variants of FGF2 molecule fused to a cytotoxic drug and validated their applicability in cell culture models. Finally, we evaluated effectiveness of FGF2-conjugates in mouse model. During the project new techniques and molecular biology methods were introduced to our laboratories, such as introduction of unnatural aminoacid into the protein sequence, site – specific conjugation of proteins with cytotoxic drugs or fluorescent molecules and ultra high resoluction confocal microscopy. Our findings were a basis of patent application registered with Polish Patent Office, and international patent application is in preparation. As for publications resulting from the project, two papers were published, and further two manuscripts were prepared for submission. Moreover, based on the results obtained within the project two master thesis and one PhD thesis were defended and two PhD thesis will be prepared.
Summary of bilateral results
Within the project we established the fruitful collaboration between Polish and Norwegian groups, providing platform for exchange of practical laboratory knowledge, experience and ideas, and sharing the results together with experimental methods between project participants. Due to the Polish-Norwegian grant excellent conditions for MS and PhD students were created to develop their scientific skills. Advanced laboratory techniques applied in both laboratories are available for young scientists. PhD students and scientists involved in the project had extraordinary opportunities to attend high quality scientific meetings, conferences and trainings to broaden their knowledge and promote the results obtained within the project. To provide the best cooperation opportunity we organized several visits and meetings, to gather Polish and Norwegian scientists together. All meetings were extremely fruitful and beneficial especially for young PhD students. There were many scientific discussions and exchange of new ideas concerning the project. Knowledge exchange and development were accompanied with social benefits. Working in closely collaborating laboratories located in different countries also influenced the cognition of different cultures and backgrounds. Both Polish and Norwegian partners are willing to continue collaboration between our laboratories. We are going to further exchange the know-how between laboratories as well as to allow young scientist to learn new technologies during onsite visits. Scientific results obtained within our project provide us basis to apply for a new joint grants. Successful cooperation of our laboratories should be encouraging for other scientists in finding foreign partners and initiating international network.