title: Pathway activation strength is a novel independent prognostic biomarker for cetuximab sensitivity in colorectal cancer patients.
abstract: Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), was shown to be active in colorectal cancer. Although some patients who harbor K-ras wild-type tumors benefit from cetuximab treatment, 40 to 60% of patients with wild-type K-ras tumors do not respond to cetuximab. Currently, there is no universal marker or method of clinical utility that could guide the treatment of cetuximab in colorectal cancer. Here, we demonstrate a method to predict response to cetuximab in patients with colorectal cancer using OncoFinder pathway activation strength (PAS), based on the transcriptomic data of the tumors. We first evaluated our OncoFinder pathway activation strength model in a set of transcriptomic data obtained from patient-derived xenograft (PDx) models established from colorectal cancer biopsies. Then, the approach and models were validated using a clinical trial data set. PAS could efficiently predict patients' response to cetuximab, and thus holds promise as a selection criterion for cetuximab treatment in metastatic colorectal cancer.
authors.affiliation: InSilico Medicine, Inc. , Baltimore, MD, USA.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Izumchenko
authors.affiliation: InSilico Medicine, Inc., Baltimore, MD, USA; Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Aliper
authors.affiliation: InSilico Medicine, Inc. , Baltimore, MD, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Makarev
authors.affiliation: Champions Oncology, Inc. , Baltimore, MD, USA.
authors.forename: Keren
authors.initials: K
authors.lastname: Paz
authors.affiliation: Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR; Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Buzdin
authors.affiliation: InSilico Medicine, Inc., Baltimore, MD, USA; Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Zhavoronkov
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky