Development of an innovative nanosystem to mediate a combined and multi-target therapeutic strategy to hepatocellular carcinoma

Overview

Project Summary

The high mortality associated to hepatocellular carcinoma (HCC), being the third largest cause of cancer mortality worldwide, shows that the present treatment options for this disease are largely unsatisfactory. Therefore, the development of new therapeutic strategies with higher efficacy and lesser side effects than those presented by conventional approaches is urgently required. There are several important molecular targets that have been associated to HCC pathogenesis. These proteins, which belong to distinct cellular signaling pathways, are overexpressed in HCC and are involved in several hepatocarcinogenic processes, such as cell survival, proliferation, differentiation, migration, invasion and immunosuppression. Therefore, these molecular targets could be the focus to the successful generation of innovative gene therapy and chemotherapy combined antitumor strategies to HCC. In this context, the main goal of this project is to generate an innovative multi-target therapeutic strategy for the treatment of HCC, consisting of a combination of gene therapy and chemotherapy, having the ability to efficiently and simultaneously abolish the multiple signaling pathways associated to the HCC pathogenesis, in order to achieve an effective and synergistic antitumor activity, with reduced side effects. To this end, a new nanosystem, composed of a new amphiphilic cationic copolymer encapsulating a chemotherapeutic agent and a DNA plasmid encoding short hairpin RNAs against HCC molecular targets, will be developed. It is expected that the novel nanosystem will have the ability to efficiently and specifically mediate this innovative multi-target therapeutic strategy, inducing a much higher antitumor activity and much less side effects, due to the specificity of the nanosystem to HCC cells, than that obtained with the conventional approaches. This research plan is a multidisciplinary project that requires a broad range of knowledge, from chemical synthesis to therapeutic evaluation. Its concretization will be ensured by a multidisciplinary team with recognized expertise in the design and synthesis of new polymers, in the development and characterization of gene and drug delivery systems, and in the generation and evaluation of new antitumor strategies.

Main Goals

The main goal of this project is to generate an innovative multi-target therapeutic strategy for the treatment of HCC, consisting of a combination of gene therapy and chemotherapy, having the ability to efficiently and simultaneously abolish the multiple signaling pathways associated to the HCC pathogenesis, in order to achieve an effective and synergistic antitumor activity, with reduced side effects.

Project Details

Project Code

PTDC/BTM-MAT/30916/2017 (POCI-01-0145-FEDER-30916)

Region

Centro

Total Cost

239884€

Financing
financier-image

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