title: Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T Y S
authors.initials: TYS
authors.lastname: Le Large
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M F
authors.initials: MF
authors.lastname: Bijlsma
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Kazemier
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: H W M
authors.initials: HWM
authors.lastname: van Laarhoven
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, Pisa, Italy; CNR-Nano, Institute of Nanoscience and Nanotechnology, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Giovannetti
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: c.jimenez@vumc.nl.
authors.forename: C R
authors.initials: CR
authors.lastname: Jimenez
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D040901:Proteomics
chemical_list: D009363:Neoplasm Proteins
keywords: Genetics; Metastasis; Pancreatic ductal adenocarcinoma; Proteomics; Transcriptomics