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NANODELIVERY OF SPECIFIC GENOME ENGINEERING TOOLS AS A NOVEL THERAPEUTIC APPROACH FOR AGGRESSIVE PROSTATE CANCERS

Project description

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.

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSIDAD DE CASTILLA - LA MANCHA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 172 932,48
Address
CALLE ALTAGRACIA 50
13071 CIUDAD REAL
Spain

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Region
Centro (ES) Castilla-La Mancha Ciudad Real
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 172 932,48
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