The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Changes in Colorectal Carcinoma Genomes under Anti-EGFR Therapy Identified by Whole-Genome Plasma DNA Sequencing
Open accessAbstract
Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we analyzed plasma DNA from ten patients treated with anti-EGFR therapy by whole genome sequencing (plasma-Seq) and ultra-sensitive deep sequencing of genes associated with resistance to anti-EGFR treatment such as KRAS, BRAF, PIK3CA, and EGFR. Surprisingly, we observed that the development of resistance to anti-EGFR therapies was associated with acquired gains of KRAS in four patients (40%), which occurred either as novel focal amplifications (n = 3) or as high level polysomy of 12p (n = 1). In addition, we observed focal amplifications of other genes recently shown to be involved in acquired resistance to anti-EGFR therapies, such as MET (n = 2) and ERBB2 (n = 1). Overrepresentation of the EGFR gene was associated with a good initial anti-EGFR efficacy. Overall, we identified predictive biomarkers associated with anti-EGFR efficacy in seven patients (70%), which correlated well with treatment response. In contrast, ultra-sensitive deep sequencing of KRAS, BRAF, PIK3CA, and EGFR did not reveal the occurrence of novel, acquired mutations. Thus, plasma-Seq enables the identification of novel mutant clones and may therefore facilitate early adjustments of therapies that may delay or prevent disease progression.
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Cites
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“Colorectal carcinomas that are wild type for KRAS are often sensitive to EGFR blockade [1,3] and therefore KRAS testing can prevent both ineffective treatment and treatment-associated toxicity.”
BackgroundPanitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer
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Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
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Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA
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Cited by
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw235 · Cited by 3,421
Liquid biopsies come of age: Towards implementation of circulating tumour DNA
Wan, J. C. M., Massie, C., Garcia-Corbacho, J., Mouliere, F., Brenton, J. D., Caldas, C., Pacey, S., Baird, R., & Rosenfeld, N. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.7 · Cited by 2,809
Comprehensive review of targeted therapy for colorectal cancer
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Current and future perspectives of liquid biopsies in genomics-driven oncology
Heitzer, E., Haque, I. S., Roberts, C. E. S., & Speicher, M. R. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0071-5 · Cited by 1,557
Self-citationClinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy
Alix-Panabières, C., & Pantel, K. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1483 · Cited by 1,394
Metadata
- Authors
- Mohan, S., Heitzer, E., Ulz, P., Lafer, I., Lax, S., Auer, M., Pichler, M., Gerger, A., Eisner, F., Hoefler, G., Bauernhofer, T., Geigl, J. B., & Speicher, M. R.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-03-27
- Volume
- 10
- Issue
- 3
- Pages
- e1004271
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W2035022458
- Cited by
- 177
- References
- 18
- FWCI
- 10.63
- Type
- journal article
- Language
- en
- Open access
- gold
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- Mohan, S., Heitzer, E., Ulz, P., Lafer, I., Lax, S., Auer, M., Pichler, M., Gerger, A., Eisner, F., Hoefler, G., Bauernhofer, T., Geigl, J. B., & Speicher, M. R. (2014). Changes in Colorectal Carcinoma Genomes under Anti-EGFR Therapy Identified by Whole-Genome Plasma DNA Sequencing. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1004271
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