title: Pathobiology of pancreatic cancer: implications on therapy.
abstract: Although the concept of tumor heterogeneity was established several decades ago, the interest in this topic is still unbroken. With the identification of inter- and intratumoral genomic rearrangements and the detection of cancer stem cells (CSCs) through phenotypic variations of cancer cells there are increasing options for pancreatic cancer therapy. Indeed, some pre-clinical studies have shown promising results in the treatment of drug-resistant CSCs, whereby a few strategies were already tested in clinical trials. Basically, CSCs are influenced by the tumor microenvironment and an epigenetic reprogramming to gain stem cell-like characteristics. Targeting options inhibiting the epithelial-mesenchymal crosstalk or promoting epigenetic-driven differentiation of CSCs to a less aggressive phenotype raised the possibilities of further therapeutic applications, which will be discussed in this review.
authors.affiliation: a Institute of Pathology , Heinrich-Heine-University , Duesseldorf , Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Regel
authors.affiliation: b Department of Surgery , Technical University , Munich , Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Hausmann
authors.affiliation: b Department of Surgery , Technical University , Munich , Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Benitz
authors.affiliation: a Institute of Pathology , Heinrich-Heine-University , Duesseldorf , Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.affiliation: c Department of Surgery , The Royal Liverpool and Broadgreen University Hospitals , Liverpool , UK.|d Department of Surgery , Heinrich-Heine-University , Duesseldorf , Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D015321:Gene Rearrangement; D006801:Humans; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: Pancreatic cancer; cancer stem cells; combination therapy; epigenetic alterations; tumor heterogeneity; tumor microenvironment