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Next-Generation Sequencing of Circulating Tumor DNA Can Optimize Second-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer after Progression on anti-EGFR Therapy: Time to Rethink Our Approach
D. Mauri, K. Kamposioras, D. Matthaios, M. Tolia, I. Nixon, M. Dambrosio, G. Zarkavelis, K. Papadimitriou, B. Petricevic, P. Kountourakis, J. Kopecky, C. Grašič Kuhar, L. Popovic, NP. Chilingirova, RA. De Mello, N. Dedić Plavetić, K. Katsanos, B....
Language English Country Switzerland
Document type Journal Article, Review
PubMed
34999585
DOI
10.1159/000521845
Knihovny.cz E-resources
- MeSH
- Circulating Tumor DNA * genetics MeSH
- Colorectal Neoplasms * drug therapy genetics pathology MeSH
- Humans MeSH
- Mutation MeSH
- Colonic Neoplasms * genetics MeSH
- Oncogenes MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. SUMMARY: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. KEY MESSAGES: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.
Department of Biomedical Sciences and Medicine University of Algarve Faro Portugal
Department of Gastroenterology University Hospital of Ioannina Ιoannina Greece
Department of Hematology and Oncology Klinik Ottakring Vienna Austria
Department of Medical Oncology Clinica San Carlo Paderno Dugnano Italy
Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands
Department of Medical Oncology Institute of Oncology Ljubljana Ljubljana Slovenia
Department of Medical Oncology The Christie NHS Foundation Trust Manchester United Kingdom
Department of Medical Oncology University of Ιoannina Ιoannina Greece
Department of Oncology Faculty of Medicine and Health Örebro University Örebro Sweden
Department of Oncology General Hospital of Rhodes Rhodes Greece
Department of Radiation Oncology University Hospital LMU Munich Munich Germany
Hospitalier Neuchâtelois La Chaux de Fonds Switzerland
Medical Oncology Department Bank of Cyprus Oncology Centre Nicosia Cyprus
Medical Oncology Department Oncology Institute of Vojvodina University of Novi Sad Novi Sad Serbia
Precision Oncology Group Federal University of São Paulo São Paulo Brazil
References provided by Crossref.org
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