AIRC 2017 - Epigenetic modifications in gene regulation: effect of 8- oxoguanine on KRAS transcription

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Titolo progetto: AIRC 2017 - Epigenetic modifications in gene regulation: effect of 8- oxoguanine on KRAS transcription

Programma di finanziamento: Bando AIRC 2017

Responsabile scientifico: prof. Luigi Xodo

Collaboratori: prof.ssa Valentina Rapozzi, Dott. Annalisa Ferino

Ruolo del DAME: proponente unico

Descrizione generale:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers with a median survival of about 6–8 months after diagnosis. Recent studies have demonstrated that point mutations in the KRAS proto-oncogene are the initial stages of PDAC development. The KRAS oncogene reprograms the metabolism of PDAC cells to generate biomass and reducing power necessary for tumour growth. As PDAC cells are addicted to mutant KRAS, this oncogene has become the focus of intense investigation. Our laboratory discovered that the KRAS promoter, upstream of the transcription start site, contains a structurally polymorphic G-rich region recognized by transcription factors regulating gene expression. This critical promoter region is viewed as an attractive target for the rational design of new anticancer molecules. The project aims to dig deeper into the regulation of the KRAS oncogene, in particular under enhanced oxidative stress conditions which are typical for cancer cells, and to identify new anticancer molecules.

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Date inizio e fine progetto: 02.01.2018 – 01.01.2023

Budget totale del progetto: 374.000,00€