TY - JOUR
T1 - Pathway activation strength is a novel independent prognostic biomarker for cetuximab sensitivity in colorectal cancer patients
AU - Zhu, Qingsong
AU - Izumchenko, Evgeny
AU - Aliper, Alexander M.
AU - Makarev, Evgeny
AU - Paz, Keren
AU - Buzdin, Anton A.
AU - Zhavoronkov, Alex A.
AU - Sidransky, David
N1 - Funding Information:
This work was supported by NIH grant SPORE P50 DE019032.
Publisher Copyright:
© 2015 The Japan Society of Human Genetics All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84943400336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943400336&partnerID=8YFLogxK
U2 - 10.1038/hgv.2015.9
DO - 10.1038/hgv.2015.9
M3 - Article
AN - SCOPUS:84943400336
SN - 2054-345X
VL - 2
JO - Human Genome Variation
JF - Human Genome Variation
IS - 1
M1 - 15009
ER -