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Inhibiting mechanotransduction for the treatment of pancreatic cancer

Descrizione del progetto

Bloccare le forze meccaniche tra cellule e microambiente per il trattamento del cancro

Le forze meccaniche tra le cellule e il loro microambiente regolano le funzioni cellulari e sono coinvolte nella tumorigenesi. L’interazione tra le molecole citoscheletriche vinculina e talina può essere inibita da un frammento di vinculina noto come VD1. Tale frammento blocca la risposta delle cellule alle forze meccaniche e l’attivazione dell’oncogene YAP (yes-associated protein, ovvero proteina associata all’enzima Yes) che si verifica nei tessuti con una rigidità meccanica anormalmente elevata. L’aumento della rigidità dei tessuti e l’attivazione di YAP favoriscono la progressione del tumore, per cui l’inibizione dell’interazione talina/vinculina potrebbe rappresentare un potenziale approccio terapeutico in diversi tipi di tumore solido. Il progetto TALVIN, finanziato dall’UE, si propone di valorizzare i farmaci peptidomimetici sintetici che riproducono l’azione della VD1 nel caso del cancro al pancreas.

Obiettivo

Mechanical forces transmitted between cells and their microenvironment drive cell function and regulate tumorigenesis. Due to this importance, our FET PROACTIVE project MECHANOCONTROL aims to understand the molecular mechanisms by which forces exert their role, and their implications in the specific application of breast cancer. In this context, we have recently identified that the interaction between the cytoskeletal molecules vinculin and talin can be inhibited by a vinculin fragment (VD1) which blocks cell response to mechanical forces, and the activation of the major oncogene YAP that occurs in tissues with abnormally high mechanical stiffness. Both increased tissue stiffness and YAP activation drive tumor progression in most solid tumors, and thus inhibiting talin/vinculin interactions has a major potential as a therapeutic approach in several solid cancer types. We have designed and synthesized peptido-mimetic drugs reproducing the action of VD1. Among those synthesized, we have identified one that inhibits the metabolism of cell lines from pancreatic, colon and prostate tumors. Our aim is to valorize these drugs in the specific case of pancreatic cancer, which is a clear unmet clinical need since it is the one with the least therapeutic alternatives and worst prognosis. Specifically, the funding from this project will pay for the national phases of the current patent (PCT/EP2017/056410), regulatory pharmacokinetics/pharmacodynamics and toxicity tests in mouse animal models, as well as for developing contacts of potential license-takers to close a license agreement. Because the focus is on pancreatic rather than breast cancer, and on bringing a specific drug to the market rather than carrying out research, this project is related to but falls out of the scope of the FET MECHANOCONTROL project.

Invito a presentare proposte

H2020-FETOPEN-2016-2017

Vedi altri progetti per questo bando

Bando secondario

H2020-FETOPEN-4-2016-2017

Meccanismo di finanziamento

CSA - Coordination and support action

Coordinatore

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Contribution nette de l'UE
€ 100 000,00
Indirizzo
CARRER BALDIRI REIXAC PLANTA 2A 10-12
08028 Barcelona
Spagna

Mostra sulla mappa

Regione
Este Cataluña Barcelona
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 100 000,00