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Research of a new antitumor compounds active against chemo-resistant tumors

Periodo
01/01/2017 - 31/12/2018
Coordinatore/trice
Prof. Roberta Fruttero
Docente
Prof. Marina Gallarate
Prof. Barbara Rolando

Aree / Gruppi di ricerca

Partecipanti al progetto

Descrizione del progetto

Members of other units:

Prof. RIGANTI Chiara

Partners:

Fondazione CRT (http://www.fondazionecrt.it/)

Sponsors: 

Description:

Cancer deaths are the second leading cause of death, after cardiovascular disease, in industrialized countries and hit millions of people every year. Among cancers, pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive cancer types, with a high incidence of distant metastasis and mortality. The main issue against successful therapy for PDAC is represented by the absence of early diagnostic markers, as well as the resistance to radiation and chemotherapies. Chemotherapy still remains the mainstay of treatment for advanced PDAC and the drug gemcitabine (GEM), used in monotherapy or in combination with other pharmacologic therapies, is the standard first-line therapeutic agent since 15 years. This project aims to synthesize novel NO-donating gemcitabine (NO-GEM) molecules conjugated with mitochondrial signals in order to improve the antitumoral efficacy of GEM in pancreas cancer in vitro and in vivo models. Our purpose consists in the overcome of PDAC resistance to GEM treatment through the strong production of mitochondrial peroxynitrite, which can kill cancer cells by oxidative stress and blocking their respiratory chain. We aim also to investigate the overall mechanisms of action of NO-GEMs and their downstream effects in PDAC cells through the analyses of both proteomic and metabolic profiles.

Keywords: Gemcitabine, Nitric Oxide; Nitric Oxide Donors; Drug Resistance; Antitumor Drugs

Links:

Ultimo aggiornamento: 21/04/2017 16:53