Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes
- PMID: 36139632
- PMCID: PMC9497075
- DOI: 10.3390/cancers14184471
Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes
Abstract
Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment.
Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus.
Results: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile.
Conclusion: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments.
Keywords: angiogenesis; biomarkers; circulating cells; everolimus; pancreatic neuroendocrine tumor.
Conflict of interest statement
C.A.C. reports personal fees from BMS and Leo Pharma, and a research grant from IPSEN (institutional). F.S. received personal fees from Ipsen, Novartis, Pfizer, Advanced Accelerator Applications, and Merck; F.S. also has institutional financial interest in GETNE, Incyte, and MSD. A.B. received fees from Novartis-AAA, Amgen, Bayer, Ipsen, Janssen, and Astellas for an advisory board and public speech. N.F. received personal fees from AAA, Hutchinson MediPharma, Merck, and Novartis; has a financial interest in 4SC, Astellas, Beigene, FIBROGEN, Incyte, IPSEN, MSD, and NUCANA; and has received research grant form IPSEN (institutional).
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- Lane H.A., Wood J.M., McSheehy P.M., Allegrini P.R., Boulay A., Brueggen J., Littlewood-Evans A., Maira S., Martiny-Baron G., Schnell C.R., et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties dis-tinct from a VEGFR tyrosine kinase inhibitor. Clin. Cancer Res. 2009;15:1612–1622. doi: 10.1158/1078-0432.CCR-08-2057. - DOI - PubMed
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