Changes in Colorectal Carcinoma Genomes under Anti-EGFR Therapy Identified by Whole-Genome Plasma DNA Sequencing

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Targeted therapies based on characteristics of the tumor genome are increasingly being offered to patients with cancer. For example, colorectal carcinomas that are wild type for KRAS are frequently treated with monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR). However, almost all patients with clinical response to anti-EGFR therapies develop resistance and underlying mechanisms are poorly understood. Because of the instability of tumor genomes the status of predictive biomarkers, such as the KRAS gene, can change during the course of disease. So-called “liquid biopsies”, e.g. analyses of circulating tumor DNA, provide genetic follow-up data non-invasively from peripheral blood. When using whole genome sequencing of plasma DNA (plasma-Seq) we observed that specific copy number changes of genes, such as KRAS, MET, or ERBB2, can be acquired under therapy and determine responsiveness to therapy. In fact, our data suggest that non-invasive genome profiling is capable of predicting responsiveness or emerging resistance to anti-EGFR therapy in the majority of cases. Hence, non-invasive testing of the current status of the tumor genome can help reduce of harm from erroneous therapeutic decisions and optimize treatment for maximal efficacy and minimal side effects, which is important for decreasing metastasized CRC-related morbidity and mortality.

Vyšlo v časopise: Changes in Colorectal Carcinoma Genomes under Anti-EGFR Therapy Identified by Whole-Genome Plasma DNA Sequencing. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004271
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004271

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