title: Translational research in neuroendocrine tumors: pitfalls and opportunities.
abstract: Interest in research on neuroendocrine tumors (NETs) has grown in the past 10 years, coinciding with improvements in our understanding of the molecular pathogenesis of NETs. In addition, NETs have become one of the most exciting settings for drug development. Two targeted agents for the management of advanced pancreatic NETs have been approved, but the development of targeted agents for NETs is limited by problems with both patient selection and demonstration of activity. In this review, we analyze these limitations and discuss ways to increase the predictive value of preclinical models for target discovery and drug development. The role of translational research and 'omics' methodologies is emphasized, with the final aim of developing personalized medicine. Because NETs usually grow slowly and metastatic tumors are found at easily accessible locations, and owing to improvements in techniques for liquid biopsies, NETs provide a unique opportunity to obtain tumor samples at all stages of the evolution of the disease and to adapt treatment to changes in tumor biology. Combining clinical and translational research is essential to achieve progress in the NET field. Slow growth and genetic stability limit and challenge both the availability and further development of preclinical models of NETs, one of the most crucial unmet research needs in the field. Finally, we suggest some useful approaches for improving clinical drug development for NETs: moving from classical RECIST-based response end points to survival parameters; searching for different criteria to define response rates (for example, antiangiogenic effects and metabolic responses); implementing randomized phase II studies to avoid single-arm phase II studies that produce limited data on drug efficacy; and using predictive biomarkers for patient selection.
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron, Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Capdevila
authors.affiliation: ProCURE Research Program, Instituto Catalán de Oncología - IDIBELL, Barcelona, Spain.
authors.forename: O
authors.identifier: 0000-0002-4298-3995
authors.initials: O
authors.lastname: Casanovas
authors.affiliation: Oncology Department, Catalan Institute of Oncology-IDIBELL, Universitat de Barcelona, Barcelona, Spain.
authors.forename: R
authors.identifier: 0000-0001-9419-6232
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Segura
authors.affiliation: Oncology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Fuster
authors.affiliation: Department of Endocrinology, Puerta de Hierro University Hospital, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Aller
authors.affiliation: Medical Oncology Department, Hospital Universitario Doce de Octubre, Center affiliated to the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: García-Carbonero
authors.affiliation: Department of Medical Oncology, Central Asturias University Hospital, Oviedo, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Jimenez-Fonseca
authors.affiliation: Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Grande
authors.affiliation: Maimónides Institute of Biomedical Research at Córdoba (IMIBIC); Reina Sofía University Hospital; Department of Cell Biology, Physiology and Immunology, University of Córdoba; CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: Castaño
mesh_terms: D044127:Epigenesis, Genetic; D052138:Genes, Neoplasm; D023281:Genomics / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D057170:Translational Research, Biomedical / Q000379:methods / Q000592:standards / Q000639:trends