Circulating hsa-miR-29c-3p and VEGF-A levels predict the response to FOLFIRI plus aflibercept in elderly metastatic colorectal cancer patients


Por: Toledano-Fonseca, M, Cano-Osuna, MT, Elez, E, Soto-Alsar, J, Paáez, D, Fernández-Montes, A, Graña, B, Salud, A, Yubero, A, Macías, I, Quintero, G, López-López, C, Fernández-Rodríguez, T, García-Ortiz, MV, Sastre, J, García-Alfonso, P, Rodríguez-Ariza, A, Aranda, E

Publicada: 17 ene 2026 Ahead of Print: 1 ago 2025
Resumen:
BackgroundMetastatic colorectal cancer (mCRC) patients who progress on oxaliplatin-based chemotherapy benefit from second-line treatment with FOLFIRI plus the antiangiogenic drug aflibercept. However, the absence of validated biomarkers for antiangiogenic therapies remains a challenge. In this context, we previously reported that combining plasma VEGF-A levels, a circulating microRNA profile, and patient clinical characteristics predicts outcomes in FOLFIRI plus aflibercept treatment. In the present study, we now report biomarkers of response to FOLFIRI plus aflibercept in elderly mCRC patients who progressed after first-line oxaliplatin-based chemotherapy.MethodsThe study included 154 mCRC patients over 70 years of age enrolled in the clinical phase II trial AFEMA. Plasma samples were obtained before FOLFIRI plus aflibercept treatment, and circulating levels of VEGF-A and 13 miRNAs were analysed.ResultsThe levels of VEGF-A and five of these 13 miRNAs (miR-193-3b, miR-432-5p, miR-29c-3p, miR-93-5p, miR-30a-3p) enabled the stratification of patients based on progression-free survival and time-to-treatment failure. Specifically, combining miR-29c-3p with VEGF-A improved prognostic accuracy.ConclusionOur study underscores the value of integrating miR-29c-3p analysis with VEGF-A as a biomarker strategy to advance the management of elderly mCRC patients receiving FOLFIRI plus aflibercept, improving outcome predictions and enabling more personalised therapeutic strategies.

Filiaciones:
Toledano-Fonseca, M:
 Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Biomed Res Inst Cordoba IMIBIC, Med Oncol Dept, Cordoba, Spain

 Canc Network Biomed Res Ctr CIBERONC, Madrid, Spain

Cano-Osuna, MT:
 Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Biomed Res Inst Cordoba IMIBIC, Med Oncol Dept, Cordoba, Spain

 Canc Network Biomed Res Ctr CIBERONC, Madrid, Spain

Elez, E:
 Univ Autonoma Barcelona, Vall dHebron Barcelona Hosp Campus, Vall dHebron Inst Oncol VHIO, Med Oncol Dept,CIBERONC, Barcelona, Spain

Soto-Alsar, J:
 Univ Complutense, Gregorio Maranon Gen Univ Hosp, Med Oncol Dept, Inst Invest Sanitaria Gregorio Maranon IiSGM, Madrid, Spain

Paáez, D:
 Hosp Santa Creu & Sant Pau, Med Oncol Dept, CIBERER, Barcelona, Spain

Fernández-Montes, A:
 Complexo Hosp Univ Ourense, Med Oncol Dept, Orense, Spain

Graña, B:
 Pontevedra Univ Hosp SERGAS, Galicia Sur Hlth Res Inst IISGS, Med Oncol Dept, Pontevedra, Spain

Salud, A:
 Hosp Univ Arnau Vilanova Lleida, Med Oncol Dept, Lleida, Spain

Yubero, A:
 Univ Hosp Lozano Blesa, Inst Hlth Res Aragon IIS Aragon, Med Oncol Dept, Zaragoza, Spain

Macías, I:
 Hosp Parc Tauli Sabadell, Med Oncol Dept, Barcelona, Spain

Quintero, G:
 Hosp Lucus Augusti, Med Oncol Dept, Lugo, Spain

López-López, C:
 Hosp Univ Marques Valdecilla, Med Oncol Dept, IDIVAL, UNICAN, Santander, Spain

Fernández-Rodríguez, T:
 Hosp Univ Son Llatzer, Med Oncol Dept, Mallorca, Spain

García-Ortiz, MV:
 Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Biomed Res Inst Cordoba IMIBIC, Med Oncol Dept, Cordoba, Spain

 Canc Network Biomed Res Ctr CIBERONC, Madrid, Spain

Sastre, J:
 Univ Complutense, Hosp Clin San Carlos, Inst Invest Hosp Clin San Carlos IdISSC, Med Oncol Dept, Madrid, Spain

García-Alfonso, P:
 Univ Complutense, Gregorio Maranon Gen Univ Hosp, Med Oncol Dept, Inst Invest Sanitaria Gregorio Maranon IiSGM, Madrid, Spain

Rodríguez-Ariza, A:
 Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Biomed Res Inst Cordoba IMIBIC, Med Oncol Dept, Cordoba, Spain

 Canc Network Biomed Res Ctr CIBERONC, Madrid, Spain

Aranda, E:
 Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Biomed Res Inst Cordoba IMIBIC, Med Oncol Dept, Cordoba, Spain

 Canc Network Biomed Res Ctr CIBERONC, Madrid, Spain
ISSN: 00142972





EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Alemania
Tipo de documento: Article
Volumen: 56 Número: 1
Páginas:
WOS Id: 001542924200001
ID de PubMed: 40747746
imagen Green Submitted, hybrid

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