Copy number load predicts outcome of metastatic colorectal cancer patients receiving bevacizumab combination therapy

Journal: Nature Communications

Published: 2018-10-05

DOI: 10.1038/s41467-018-06567-6

Affiliations: 27

Authors: 33

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Research Highlight

A precision oncology test for colorectal cancer

© theasis/Getty

© theasis/Getty

The extent to which large stretches of a tumour cell’s DNA are duplicated or deleted may help doctors identify which colorectal cancer patients are good candidates for treatment with bevacizumab, a best-selling drug that chokes the blood supply to tumours.

Nowadays, many oncologists routinely prescribe bevacizumab alongside chemotherapy for advanced cases of this common and deadly cancer, even though the drug, which is marketed as Avastin, works just for a minority of patients.

A genetic test that predicts which patients would benefit from the drug could help spare others needless exposure to the bevacizumab’s powerful, and toxic, effects, which include complications such as bleeding episodes, arterial clotting events, elevated blood pressure and defective wound healing.

Furthermore, a test for alterations in DNA copy numbers — a genomic situation called ‘chromosomal instability’ — could help lower healthcare expenses in places that already use the life-extending therapy to treat colorectal cancer. And it could expand patient access in countries that have restricted the use of bevacizumab, citing the drug’s lack of cost effectiveness when offered across the board to those with metastatic colorectal cancer.

Genetic profiling of colorectal tumours is “now poised to impact clinical treatment paradigms,” Annette Byrne of the Royal College of Surgeons in Ireland told attendees of the 2018 International Conference on Gastro Education. Her team’s findings, she noted, show that “chromosomal instability represents a novel biomarker for bevacizumab response.”

Byrne is the project coordinator of ANGIOPREDICT, a European initiative geared at personalizing the use of bevacizumab among colorectal cancer patients. Members of that research consortium had previously shown that tumours lacking a large chunk of chromosome 18 were particularly sensitive to bevacizumab treatment. It now seems that specific loss of DNA seems to be just one example of a much larger genomic phenomenon.

Byrne and her colleagues analysed the DNA of archived tumour samples from more than 400 individuals with colorectal cancer. They concluded that patients with intermediate-to-high levels of chromosomal instability in their tumours responded favourably to the combination of bevacizumab plus chemotherapy, whereas patients with low-instability tumours derived no further benefit from the addition of bevacizumab to standard treatment. The researchers also confirmed the findings in mouse models.

Looking ahead, Byrne noted that there’s already a movement among colorectal cancer experts to reclassify the disease into subtypes according to genomic profiles. Within that framework, she said, genetic testing should become more routine and the personalization of bevacizumab-related treatment decisions should follow.

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  1. Nature Communications 9, 4112 (2018). doi: 10.1038/s41467-018-06567-6
Institutions FC
Department of Physiology and Medical Physics, RCSI, Ireland 0.13
VIB-KU Leuven Center for Cancer Biology (CCB), Belgium 0.07
UCD School of Biomolecular and Biomedical Science (SBBS), Ireland 0.07
UCD Conway Institute of Biomolecular and Biomedical Research, Ireland 0.07
University Medical Centre Mannheim (UMM), Uni Heidelberg, Germany 0.06
VUmc Cancer Center Amsterdam (CCA), Netherlands 0.06
Department of Surgery, Beaumont Hospital, Ireland 0.06
Department of Human Genetics, KU Leuven, Belgium 0.06
Department of Medical Oncology, VUmc, Netherlands 0.05
OncoMark Ltd., Ireland 0.04
University Medical Center Utrecht (UMC Utrecht), Netherlands 0.03
Cancer Trials Ireland, Ireland 0.03
Department of Pathology, Beaumont Hospital, Ireland 0.03
UCD School of Veterinary Medicine, Ireland 0.03
IRCCS Istituto Oncologico Veneto (IOV), Italy 0.03
Institute of Pathology, UMM, Germany 0.03
Department of Pathology, VU University Amsterdam, Netherlands 0.03
Department of Molecular and Cellular Therapeutics (MCT), RCSI, Ireland 0.02
Department of Oncology, KU Leuven, Belgium 0.02
Center for Oncological Research (CORE), UA, Belgium 0.02
Istituto Toscano Tumori (ITT), Italy 0.02
Department of Translational Research and New Technologies in Medicine and Surgery, UNIPI, Italy 0.02
University of Amsterdam (UvA), Netherlands 0.02
Antwerp University Hospital (UZA), UA, Belgium 0.02
Department of Gynaecology and Obstetrics, UZ Leuven, Belgium 0.01