title: An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs).
abstract: Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease.
authors.affiliation: Medical Oncology Department, Ramón y Cajal University Hospital, Ctra. Colmenar Viejo km 9100, 28034 Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Alonso-Gordoa
authors.affiliation: Endocrinology and Nutrition Department, Ramón y Cajal University Hospital, Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Díez
authors.affiliation: Medical Oncology Department, Ramón y Cajal University Hospital, Ctra. Colmenar Viejo km 9100, 28034 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Molina
authors.affiliation: Medical Oncology Department, Ramón y Cajal University Hospital, Ctra. Colmenar Viejo km 9100, 28034 Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Reguera
authors.affiliation: Medical Oncology Department, Ramón y Cajal University Hospital, Ctra. Colmenar Viejo km 9100, 28034 Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Martínez-Sáez
authors.affiliation: Medical Oncology Department, Ramón y Cajal University Hospital, Ctra. Colmenar Viejo km 9100, 28034 Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Grande
keywords: Chemotherapy; Molecular biology; Pancreatic neuroendocrine tumor; Resistance mechanisms; Sequencing; Somatostatin analogs; Targeted agents; pNET