Sistema de Salut de Catalunya
Institut Català de la Salut
[Toledano-Fonseca M] Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain. Cancer Network Biomedical Research Center (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Gómez-España MA, Rodríguez R] Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain. Department of Medical Oncology, Reina Sofía University Hospital, Córdoba, Spain. [Élez E, Tabernero JM] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Grávalos C] Department of Medical Oncology, H. Universitario 12 de Octubre, Instituto de Investigación i+12, Avenida de Córdoba, Madrid, Spain. [García-Alfonso P] Department of Medical Oncology, H. Gregorio Marañón, Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-03-08T13:23:09Z
2023-03-08T13:23:09Z
2023-03
Antiangiogenic therapy; Circulating miRNAs; Colorectal cancer
Terapia antiangiogénica; MiARN circulantes; Cáncer colorrectal
Teràpia antiangiogènica; MiARN circulants; Càncer colorectal
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.
Funding was provided by Sanofi.
Article
Published version
English
Còlon - Càncer - Tractament; Recte - Càncer - Tractament; Quimioteràpia combinada; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada; COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN
Elsevier
Biomedicine & Pharmacotherapy;159
https://doi.org/10.1016/j.biopha.2023.114272
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Articles científics - HVH [3440]
