Project description DEENESFRITPL Multi-functional nanoparticles as a novel approach for prostate cancer treatment Prostate cancer primary tumours respond well to treatment but in the advanced stage become inherently resistant to chemotherapy. The current treatment for advanced prostate cancer consists of androgen deprivation therapy and docetaxel (DTX) chemotherapy. DTX can inhibit androgen receptor (AR) signalling, but at the same time, the activation of AR signalling can induce DTX insensitivity. The EU-funded NANOCRISPR project proposes to break this dependency of DTX effectiveness on AR signalling and ensure efficient treatment for advanced prostate cancer using the selective inhibition of AR by CRISPR/Cas9 technology together with DTX. Both therapeutic approaches will be encapsulated into prostate-specific targeted nanoparticles for the simultaneous delivery of the drug and CRISPR plasmids targeting AR into the tumour. Show the project objective Hide the project objective Objective Prostate cancer is the second most common diagnosed malignancy and the fifth leading cause of cancer mortality in men. Whilst primary tumours respond well to therapy, tumours in the metastatic setting become inherently resistant to chemotherapy. Thus, more novel and effective therapeutic approaches are highly needed to treat this lethal disease.The cornerstone treatment for advanced prostate cancer consists of androgen deprivation therapy and docetaxel (DTX). However, both DTX activity and Androgen receptor (AR) signalling are highly interrelated. On the one hand, it has been shown that DTX is able to inhibit Androgen Receptor (AR) signalling and on the other hand, the activation of AR signaling can induce DTX insensitivity. In order to break this dependency of DTX effectiveness on AR signaling and ensure efficient treatment for advanced prostate cancer, we propose the selective inhibition of AR deploying CRISPR/Cas9 technology together with DTX. Both therapeutical approaches will be encapsulated into prostate-specific targeted nanoparticles which will allow the simultaneous delivery of the drug and CRISPR plasmids targeting AR into the tumour site. The designed state-of-art multi-functional nanoparticles will reprogram and sensitise the prostate tumour to DTX in situ, and will also induce a higher accumulation of the treatment in the tumour while healthy tissues will remain less affected. Moreover, the use of CRISPR/Cas9 will precisely engineer the prostate cancer cells to express lower levels of AR, contrasting with current anti-AR treatments, which have multiple off-targets.This approach represents an innovative targeted therapy for advanced prostate cancer. It will allow the administration of lower doses of chemotherapy with consequently reduced toxicity and the potential for longer tolerated treatment periods, whilst improving efficacy by selectively suppressing the molecular pathways causing cancer survival and resistance to treatment. Fields of science medical and health sciencesclinical medicineoncologyprostate cancersocial sciencessociologydemographymortalityengineering and technologynanotechnologynano-materialsnatural sciencesbiological sciencesgeneticsgenomes Keywords NANOCRISPR 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-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSIDAD DE CASTILLA - LA MANCHA Net EU contribution € 172 932,48 Address Calle altagracia 50 13071 Ciudad real Spain See on map Region Centro (ES) Castilla-La Mancha Ciudad Real Activity type Higher or Secondary Education Establishments 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
