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Riera P, Rodríguez-Santiago B, Lasa A, et al. Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients. Cancers (Basel). 2020;12(8)doi: 10.3390/cancers12082245.
Riera, P., Rodríguez-Santiago, B., Lasa, A., Gonzalez-Quereda, L., Martín, B., Salazar, J., Sebio, A., Virgili, A. C., Minguillón, J., Camps, C., Surrallés, J., & Páez, D. (2020). Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients. Cancers, 12(8), . https://doi.org/10.3390/cancers12082245
Riera, Pau, et al. "Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients." Cancers vol. 12,8 (2020). doi: https://doi.org/10.3390/cancers12082245
Riera P, Rodríguez-Santiago B, Lasa A, Gonzalez-Quereda L, Martín B, Salazar J, Sebio A, Virgili AC, Minguillón J, Camps C, Surrallés J, Páez D. Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients. Cancers (Basel). 2020 Aug 11;12(8). doi: 10.3390/cancers12082245. PMID: 32796636; PMCID: PMC7463997.
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Cancers (Basel). 2020 Aug 11;12(8). doi: 10.3390/cancers12082245.

Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients.

Cancers

Pau Riera, Benjamín Rodríguez-Santiago, Adriana Lasa, Lidia Gonzalez-Quereda, Berta Martín, Juliana Salazar, Ana Sebio, Anna C Virgili, Jordi Minguillón, Cristina Camps, Jordi Surrallés, David Páez

Affiliations

  1. Genetics Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
  2. Pharmacy Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
  3. Faculty of Pharmacy and Food Sciences, Universitat de Barcelona (UB), 08028 Barcelona, Spain.
  4. Join Research Unit on Genomic Medicine UAB-IR Sant Pau, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
  5. U705 and U745, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), 08041 Barcelona, Spain.
  6. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
  7. Translational Medical Oncology Laboratory, Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), 08041 Barcelona, Spain.
  8. Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

PMID: 32796636 PMCID: PMC7463997 DOI: 10.3390/cancers12082245

Abstract

BACKGROUND: About 40% of

PATIENTS AND METHODS: Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results.

RESULTS: Among 61 patients, 38 were sensitive and 23 were resistant to treatment. We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in

CONCLUSIONS: This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and

Keywords: anti-EGFR monoclonal antibodies; case-control study; colorectal cancer; genetic variants; predictive biomarkers

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