Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2020; 12(3): 301-310
Published online Mar 15, 2020. doi: 10.4251/wjgo.v12.i3.301
Circulating cytokines and outcome in metastatic colorectal cancer patients treated with regorafenib
Vincenzo Ricci, Cristina Granetto, Antonella Falletta, Matteo Paccagnella, Andrea Abbona, Elena Fea, Teresa Fabozzi, Cristiana Lo Nigro, Marco Carlo Merlano
Vincenzo Ricci, Cristina Granetto, Elena Fea, Marco Carlo Merlano, Medical Oncology and Laboratory of Translational Oncology, Oncology Department, S. Croce and Carle Teaching Hospital Cuneo, Cuneo 12100, Italy
Antonella Falletta, Matteo Paccagnella, Andrea Abbona, Marco Carlo Merlano, Arco Cuneo Foundation, Cuneo 12100, Italy
Teresa Fabozzi, Medical Oncology, S. G. Bosco Hospital, Torino 10154, Italy
Cristiana Lo Nigro, Laboratory, S. Croce and Carle Teaching Hospital Cuneo, Cuneo 12100, Italy
Author contributions: Ricci V and Merlano MC designed the research; Ricci V, Granetto C and Fea E enrolled the patients; Fabozzi T, Granetto C and Lo Nigro C revised the manuscript; Falletta A, Paccagnella M and Abbona A performed the research; Lo Nigro C collected the samples; Falletta A, Ricci V and Fabozzi T wrote the paper and Paccagnella M analyzed the data; Merlano MC revised the manuscript for important intellectual content.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
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: Vincenzo Ricci, MD, Doctor, Medical Oncology and Laboratory of Translational Oncology, Oncology Department, S. Croce and Carle Teaching Hospital, Via A. Carle 5, Cuneo 12100, Italy. vincenzoricci22@libero.it
Received: November 14, 2019
Peer-review started: November 14, 2019
First decision: November 18, 2019
Revised: February 7, 2020
Accepted: February 17, 2020
Article in press: February 17, 2020
Published online: March 15, 2020
BACKGROUND
Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer (mCRC). Regorafenib has shown significant benefits in overall survival and progression free survival in two phase III trials compared to placebo in patients with mCRC who had progressed on previous therapy.
AIM
To identify an immune profile that might specifically correlate with the outcome in patients treated with regorafenib.
METHODS
Blood samples were collected from 17 patients before treatment with regorafenib and from 6 healthy volunteers. The proteins evaluated (TNF-α, TGF-β, VEGF, CCL-2, CCL-4, and CCL-5) were selected on the basis of their roles in angiogenesis and colorectal cancer pathogenesis.
RESULTS
We found that TNF-α basal level was significantly higher in mCRC patients compared to healthy individuals. Non Responder (NR) patients showing progression of disease (n = 12) had higher basal level of TGF-β, TNF-α, VEGF, CCL-2 and CCL-5 compared to Responder (R) patients (complete response CR, n = 1; partial response PR, n = 1; Stable Disease SD, n = 3). On the contrary, plasma basal level of CCL-4 was higher in R compared to NR patients. High values of TGF-β and TNF-α negatively correlated with progression free survival.
CONCLUSION
These results suggest a cytokine signature potentially able to discriminate between R and NR patients to treatment with regorafenib.
Core tip: We analyzed levels of specific cytokines in plasma of metastatic colorectal cancer patients before treatment with regorafenib. Our aim was to identify biomarkers useful to select metastatic colorectal cancer responder patients and an immune profile potentially correlated with the outcome.
