Case Report
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2016; 22(48): 10680-10686
Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10680
Efficiency of olaparib in colorectal cancer patients with an alteration of the homologous repair protein
Francois Ghiringhelli, Corentin Richard, Sandy Chevrier, Frédérique Végran, Romain Boidot
Francois Ghiringhelli, Department of Medical Oncology, Center GF Leclerc, 21000 Dijon, France
Francois Ghiringhelli, Corentin Richard, Sandy Chevrier, Frédérique Végran, Romain Boidot, Platform of Transfer in Oncology, Center GF Leclerc, 21000 Dijon, France
Francois Ghiringhelli, Romain Boidot, Frederique Vegran, INSERM UMR866, 21000 Dijon, France
Francois Ghiringhelli, Corentin Richard, University of Bourgogne Franche Comte, 21000 Dijon, France
Author contributions: Ghiringhelli F and Boidot R designed the report; Richard C, Chevrier S and Végran F performed the genetic analyses; Ghiringhelli F collected the patient’s clinical data; Ghiringhelli F and Boidot R analyzed the data and wrote the paper.
Institutional review board statement: This study was approved by the local institutional review board.
Informed consent statement: Patients gave their written consent to authorize genetic analyses.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Francois Ghiringhelli, MD, PhD, Professor, Department of Medical Oncology, Center GF Leclerc, 21000 Dijon, France. fghiringhelli@cgfl.fr
Telephone: +33-380393371 Fax: +33-380393434
Received: July 7, 2016
Peer-review started: July 11, 2016
First decision: August 22, 2016
Revised: August 26, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: December 28, 2016
Processing time: 171 Days and 19.2 Hours
Abstract

Precision medicine is defined by the administration of drugs based on the tumor’s particular genetic characteristics. It is developing quickly in the field of cancer therapy. For example, KRAS, NRAS and BRAF genetic testing demonstrates its efficiency for precision medicine in colorectal cancer (CRC). Besides for these well-known mutations, the purpose of performing larger genetic testing in this pathology is unknown. Recent reports have shown that using the poly ADP ribose polymerase (PARP) inhibitor olaparib in patients with homologous repair enzyme deficiency gave positive clinical results in breast, ovarian and prostate cancers. We have reported here the cases of 2 patients with multi-treated metastatic CRC who underwent somatic and constitutional exome analyses. The analyses revealed a loss of function mutation in a homologous repair enzyme resulting in the loss of heterozygosity for both patients (Check2 for the first patient and RAD51C for the second one). Both patients were treated with off-label usage of olaparib. While the first patient showed clinical benefit, reduction of carcinoembryonic antigen tumor marker and radiologic response, the second patient quickly presented a progression of the tumor. Additional genetic analyses revealed a frameshift truncating mutation of the TP53BP1 gene in the patient who progressed. Interestingly, deficiency in TP53BP1 was previously described to confer resistance to olaparib in mice breast cancer models. Our findings suggest that exome analysis may be a helpful tool to highlight targetable mutations in CRC and that olaparib may be efficient in patients with a homologous repair deficiency.

Keywords: Colorectal cancer; Exome analysis; Genetic aberrations; Homologous repair deficiency; Precision medicine

Core tip: The role of genetic profiling in metastatic colorectal cancer for precision medicine is currently under investigation. This case report underlines for the first time, that olaparib may have some clinical efficiency in patients with homologous repair deficiency in colorectal tumor.