RT Journal Article
T1 Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study.
A1 Conde, Elisa
A1 Earl, Julie
A1 Crespo-Toro, Lorena
A1 Blanco-Agudo, Carolina
A1 Ramos-Muñoz, Edurne
A1 Rodriguez-Serrano, E Macarena
A1 Martinez Avila, Jose Carlos
A1 Salinas-Muñoz, Laura
A1 Serrano-Huertas, Silvia
A1 Ferreiro, Reyes
A1 Rodriguez-Garrote, Mercedes
A1 Sainz, Bruno
A1 Massuti, Bartomeu
A1 Alfonso, Pilar Garcia
A1 Benavides, Manuel
A1 Aranda, Enrique
A1 Garcia-Bermejo, Maria Laura
A1 Carrato, Alfredo
K1 Biomarkers
K1 Colorectal cancer
K1 miRNAs
K1 Regorafenib
K1 Toxicity
K1 Treatment response
AB First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. In conclusion, VEGF and VEGFR SNPs, miRNAs, and Notch 1 levels are potential useful biomarkers for the management of advanced CRC under regorafenib treatment.
PB MDPI
SN 2072-6694
YR 2021
FD 2021-03-30
LK http://hdl.handle.net/10668/17660
UL http://hdl.handle.net/10668/17660
LA en
NO Conde E, Earl J, Crespo-Toro L, Blanco-Agudo C, Ramos-Muñoz E, Rodríguez-Serrano EM, et al. Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study. Cancers (Basel). 2021 Apr 4;13(7):1710
DS RISalud
RD Apr 6, 2025