A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients

Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved..

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:159

Enthalten in:

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 159(2023) vom: 05. März, Seite 114272

Sprache:

Englisch

Beteiligte Personen:

Toledano-Fonseca, M [VerfasserIn]
Gómez-España, M A [VerfasserIn]
Élez, E [VerfasserIn]
Grávalos, C [VerfasserIn]
García-Alfonso, P [VerfasserIn]
Rodríguez, R [VerfasserIn]
Losa, F [VerfasserIn]
Alés Díaz, I [VerfasserIn]
Graña, B [VerfasserIn]
Valladares-Ayerbes, M [VerfasserIn]
García-Ortiz, M V [VerfasserIn]
Polo, E [VerfasserIn]
Salgado, M [VerfasserIn]
Rivera, F [VerfasserIn]
Safont, M J [VerfasserIn]
Salud, A [VerfasserIn]
Ruiz-Casado, A [VerfasserIn]
Tabernero, J M [VerfasserIn]
Riesco, M C [VerfasserIn]
Rodríguez-Ariza, A [VerfasserIn]
Aranda, E [VerfasserIn]
Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) [VerfasserIn]

Links:

Volltext

Themen:

15C2VL427D
Aflibercept
Antiangiogenic therapy
Biomarkers
Camptothecin
Circulating MicroRNA
Circulating miRNAs
Colorectal cancer
EC 2.7.10.1
Fluorouracil
Journal Article
Leucovorin
MicroRNAs
Q573I9DVLP
Receptors, Vascular Endothelial Growth Factor
Recombinant Fusion Proteins
U3P01618RT
XT3Z54Z28A

Anmerkungen:

Date Completed 07.02.2023

Date Revised 07.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.biopha.2023.114272

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM352170905