Mini-Reviews and PerspectivesPancreatic Cancer Development and Progression: Remodeling the Model
Section snippets
What Is the Best Evidence for the Linear Progression Model?
The study of human tissue samples is necessarily a snapshot of tumor progression. Therefore, establishment of phylogenetic relationships is possible only when a genetic event that occurs with a low frequency and displays individual tumor specificity is present in lesions representative of various tumor developmental stages. Even then, the relationship between the tumor and the preneoplastic lesions present nearby is questionable.
The increasing prevalence of a given molecular alteration with
Senescence: A Mechanism for Tumor Suppression
In the past few years, cellular senescence has been recognized as a process of permanent cell cycle exit in response to several types of stress, including oxidative stress, DNA damage, oncogenic stress, chemotherapeutic drugs, and telomere attrition.16 Senescence has emerged as a protective mechanism against tumor progression. The first evidence of a cellular checkpoint triggered by exogenous oncogene expression came from the observation that primary mouse embryo fibroblasts undergo senescence
Conclusion
The genetic evidence on the progression model of PDAC has been accepted widely as linear. However, there are alternative interpretations, especially in light of knowledge about OIS in vitro and in vivo. It may be time to revisit the current model of PDAC development and progression. The major impact of improved knowledge about PDAC progression will be a better appreciation of precursor lesions that evolve to PDAC and identification of patients at increased risk for PDAC.
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Work in the authors' laboratory is supported, in part, by grants from the Ministerio de Educación y Ciencia (SAF2007-60860 and Consolider ONCOBIO) and European Union Biomed Programme (QLG-CY-2002-01196) and grant MolDiag-PaCa from the VIth Framework Programme.