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Targeting Angiogenesis in Pancreatic Neuroendocrine Tumors: Resistance Mechanisms.

Authors
  • Pozas, Javier1
  • San Román, María2
  • Alonso-Gordoa, Teresa3, 4, 5
  • Pozas, Miguel6
  • Caracuel, Laura7
  • Carrato, Alfredo8, 9, 10
  • Molina-Cerrillo, Javier11, 12, 13
  • 1 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 2 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 3 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 4 The Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, 28034 Madrid, Spain. [email protected] , (Spain)
  • 5 Alcalá University, 28805 Madrid, Spain. [email protected] , (Spain)
  • 6 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 7 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 8 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 9 The Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, 28034 Madrid, Spain. [email protected] , (Spain)
  • 10 Alcalá University, 28805 Madrid, Spain. [email protected] , (Spain)
  • 11 Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain. [email protected] , (Spain)
  • 12 The Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, 28034 Madrid, Spain. [email protected] , (Spain)
  • 13 Alcalá University, 28805 Madrid, Spain. [email protected] , (Spain)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Oct 08, 2019
Volume
20
Issue
19
Identifiers
DOI: 10.3390/ijms20194949
PMID: 31597249
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Despite being infrequent tumors, the incidence and prevalence of pancreatic neuroendocrine tumors (P-NETs) has been rising over the past few decades. In recent years, rigorous phase III clinical trials have been conducted, allowing the approval of several drugs that have become the standard of care in these patients. Although various treatments are used in clinical practice, including somatostatin analogues (SSAs), biological therapies like sunitinib or everolimus, peptide receptor radionuclide therapy (PRRT) or even chemotherapy, a consensus regarding the optimal sequence of treatment has not yet been reached. Notwithstanding, sunitinib is largely used in these patients after the promising results shown in SUN111 phase III clinical trial. However, both prompt progression as well as tumor recurrence after initial response have been reported, suggesting the existence of primary and acquired resistances to this antiangiogenic drug. In this review, we aim to summarize the most relevant mechanisms of angiogenesis resistance that are key contributors of tumor progression and dissemination. Furthermore, several targeted molecules acting selectively against these pathways have shown promising results in preclinical models, and preliminary results from ongoing clinical trials are awaited.

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