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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and CXCL5 expression: Six case reports
Apolonia Novillo, María Gaibar, Alicia Romero-Lorca, María Fuencisla Gilsanz, Laura Beltrán, Miguel Galán, Beatriz Antón, Diego Malón, Amalia Moreno, Ana Fernández-Santander
Apolonia Novillo, Department of Pre-clinical Dentistry, Health Sciences Faculty, Universidad Europea de Madrid, Villaviciosa de Odón, Madrid 28670, Spain
María Gaibar, Laura Beltrán, Miguel Galán, Department of Health Sciences, Health Sciences Faculty, Universidad Europea de Madrid, Villaviciosa de Odón, Madrid 28670, Spain
Alicia Romero-Lorca, María Fuencisla Gilsanz, Ana Fernández-Santander, Department of Medicine, Health Sciences Faculty, Universidad Europea de Madrid, Villaviciosa de Odón, Madrid 28670, Spain
Beatriz Antón, Diego Malón, Department of Oncology, University Hospital of Fuenlabrada, Fuenlabrada, Madrid 28942, Spain
Amalia Moreno, Department of Pathological Anatomy, University Hospital of Fuenlabrada, Fuenlabrada, Madrid 28942, Spain
Author contributions: Fernández-Santander A wrote the project to obtain funding, managed meetings between the university and hospital, reviewed the literature and drafted the manuscript; Malón D and Antón B were the patients' oncologists, reviewed the literature and contributed to manuscript drafting; Moreno A was responsible for paraffinating biopsy specimens and obtaining cuts; Galán M, Beltrán L and Gilsanz MF performed RNA isolation and purification procedure and reviewed the literature; Novillo A, Romero-Lorca A and Gaibar M conducted the genetic expression analysis and revised the intellectual content of the manuscript; all authors issued their final approval of the version to be submitted.
Supported by University Hospital of Fuenlabrada, Universidad Europea de Madrid (project numbers 2015/UEM12 and 2016/UEM13) and Fundación de la Universidad Europea (project numbers FGUE001804 and FGUE001805).
Informed consent statement: Informed written consent was obtained from the patients for publication of this report.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ana Fernández-Santander, PhD, Full Professor, Research Scientist, Senior Researcher, Department of Medicine, Health Sciences Faculty, Universidad Europea de Madrid, Tajo, Villaviciosa de Odón, Madrid 28670, Spain.
ana.fernandez@universidadeuropea.es
Received: January 7, 2020
Peer-review started: January 7, 2020
First decision: February 19, 2020
Revised: March 26, 2020
Accepted: April 17, 2020
Article in press: April 17, 2020
Published online: April 28, 2020
Processing time: 111 Days and 14.2 Hours
BACKGROUND
In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment.
CASE SUMMARY
We report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment.
CONCLUSION
A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.
Core tip: Although compared to chemotherapy (CT) alone, bevacizumab-containing CT leads to a significantly better tumor response in metastatic colorectal cancer patients, many do not benefit from this regimen probably due to resistance mechanisms or readjustment of proangiogenic pathways. While CXCL5 expression has been described to predict a poor prognosis in different cancers, its relationship with the efficacy of CT regimens has been scarcely addressed. Our three patients showing CXCL5 higher expression (6 times the levels recorded in the others) showed a poor response in terms of progression-free survival. Our observations provide direction for future studies designed to examine in metastatic colorectal cancer patients treated with bevacizumab-containing therapy, the possible association between CXCL5 gene overexpression and a poor response to treatment with angiogenic drugs.
