CAM-PAC

Integrative Analysis of Gene Functions in Cellular and Animal Models of Pancreatic Cancer

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 Obiettivo del progetto (Objective)

'Cancers are genetic disease arising from the accumulation of multiple molecular alterations in affected cells. Large-scale genomic, transcriptomic and proteomic analyses have established comprehensive catalogues of molecules which are altered in their structure and/or abundance in malignant tumors as compared to healthy tissues. Far less developed are concepts and methods to integrate data from different sources and to directly interrogate gene functions on a large scale in order to differentiate “driver” alterations, which directly contribute to tumor progression, from indolent “passenger” alterations. As a consequence, examples of successful translation of knowledge generated from “omics” approaches into novel clinical concepts and applications are scarce. Pancreatic cancer is a prime example of this dilemma. Representing the 4th to 5th most common cause of cancer related deaths, it is a disease with a major socioeconomic impact. Despite enormous advances in the identification of molecular changes associated with the disease, new treatment options have not emerged. Thus, 5-year survival rates remain unchanged at a dismal 6%, the lowest for all solid tumors. Using pancreatic cancer as a model disease, the goal of this integrative project is to develop novel cellular and animal models, as well as novel strategies to generate, analyze and integrate large scale metabolic and transcriptomic data from these models, in order to systematically characterize and validate novel targets for therapeutic intervention. In addition to the general tumor cell population, special consideration will be given to sub-populations of tumor-initiating cells, a.k.a. tumor stem cells. To this end, the consortium comprises i) SMEs with strong focus on technology development, ii) clinical and academic partners with extensive experience in pancreatic cancer molecular biology and management of pancreatic cancer patients, and iii) technology and data analysis experts from academic groups.'

Introduzione (Teaser)

Cancer arises from the accumulation of multiple molecular alterations. To develop novel treatments we need to understand how malignant cells differ at the molecular level from their healthy counterparts.

Descrizione progetto (Article)

Pancreatic ductal adenocarcinoma (PDAC) ranks amongst the most common cancers and has very dismal prognosis with a five year survival rate of only 6 %. It is virtually resistant to any conventional therapeutic regimens. Despite advances in the identification of molecular alterations in PDAC very little of this knowledge has been translated into novel treatments.

The EU-funded http://www.cam-pac.eu/ (CAM-PAC) (Integrative analysis of gene functions in cellular and animal models of pancreatic cancer) project aims to identify novel targets for therapeutic intervention and develop bioinformatic models for predictive diagnostics. The consortium will develop novel cellular and animal models of the disease and perform a large-scale analysis of metabolic, transcriptomic and genetic data from these models.

The generated cellular and animal tools will carry modifications in certain target genes to assess affected signalling pathways. Systematic functional characterisation of target genes relies on novel technologies for temporal and spatial control of transgene expression. Scientists will identify the functions of these genes and monitor their impact on tumourigenicity. So far, a central growth-regulatory role of many of the selected target genes has been demonstrated in vitro.

In addition to these experimental models of PDAC, the project will analyse primary human tissues at the molecular level. To address the inter- and intra-tumour heterogeneity in human PDAC, scientists will also use xenografts from patient samples.

The findings of the study are anticipated to contribute to a better understanding of the disease, identify new compounds and therapeutic targets for PDAC. Considering the annual increase of PDAC incidence, innovative diagnostic and treatment approaches are urgently needed to prolong survival and reduce the suffering of pancreatic cancer patients.