Objective Standard of care strategies for the treatment of cancer still relies heavily on non-specific radiation and chemotherapy. These treatments are commonly associated with severe toxicities and in many cases only offer limited benefit for the patient. The targeted delivery of radionuclides, cytotoxic drugs and pro-inflammatory cytokines into malignant tissue, on the other hand, can markedly improve the therapeutic index and overall efficacy of such substances. Whilst monoclonal antibodies are the most widely used delivery vehicles to date, low molecular weight targeted agents are emerging as a promising alternative to antibody-based drug delivery. These ligands have negligible immunogenic risk and are easier to chemically modify enabling fine tuning of their ADME profile. As a result, it is possible to achieve a time dependent release of the cytotoxic payload at the target tissue maximizing its therapeutic efficacy while producing minimal damage to healthy cells. Most importantly, depth of tumour penetration and tumour-to-blood distribution ratio after injection should be significantly superior.We therefore propose to systematically investigate the targeting performance of bone marrow tyrosine kinase in chromosome X (BMX) ligands for the targeted delivery of cytotoxic drugs into BMX-overexpressing tumours, namely prostate cancer. This project aims at (1) demonstrate that a BMX ligand can selectively accumulate in BMX-overexpressing cancers; (2) developing a general chemical approach for building safe ligand-drug conjugates (LDCs); and (3) when site-specifically conjugated to cytotoxic drug, this novel LDC is highly effective for the treatment of prostate cancer. This project is expected to explore new avenues for drug delivery systems since the concepts here proposed go beyond prostate cancer therapy as they can be applicable to any ligand that interferes with up-regulated disease-related pathways. Fields of science medical and health sciencesclinical medicineoncologyprostate cancernatural sciencesbiological sciencesgeneticschromosomesnatural scienceschemical sciencesnuclear chemistryradiation chemistry Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES Net EU contribution € 160 635,60 Address Avenida prof egas moniz 1649 028 Lisboa Portugal See on map Region Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
