Targeting Angiogenesis in Pancreatic Neuroendocrine Tumors: Resistance Mechanisms.
Int J Mol Sci
; 20(19)2019 Oct 08.
Article
in En
| MEDLINE
| ID: mdl-31597249
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Neuroendocrine Tumors
/
Angiogenesis Inhibitors
/
Molecular Targeted Therapy
/
Neovascularization, Pathologic
/
Antineoplastic Agents
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2019
Document type:
Article
Affiliation country:
Spain