Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan.

Seung Tae Kim,Se Hoon Park,Ho Yeong Lim,Suk Hyeong Kim,Eunjin Lee,Won Ki Kang,Tae Jin Ahn,Young Suk Park,Jeeyun Lee,Joon Oh Park,In-Gu Do,Su Jin Lee,Hee Cheol Kim

doi:10.1186/s12885-015-1759-y

Abstract

BackgroundMore than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC.MethodsWe investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes.ResultsBRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS.ConclusionThe result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC.

Highlights

More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer
Following the discovery that mutations in KRAS are associated with resistance to anti-epidermal growth factor receptor (EGFR) treatment, determination of KRAS status is recommended in metastatic colorectal cancer (mCRC) patients before starting anti-EGFR therapies
Our analysis suggested that the overexpression of PSKH1, TLK2 and PHKG2 may be a considered a potential biomarker to predict the efficacy of cetuximab plus irinotecan (CI) in wild type KRAS Colorectal cancer (CRC)

Summary

Introduction

More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). Metastatic CRC (mCRC) is associated with a poor prognosis. Only 10–20 % of the selected mCRC patients benefit from anti-EGFR therapy [3,4,5,6], highlighting a distinct need for individualized treatment. Following the discovery that mutations in KRAS are associated with resistance to anti-EGFR treatment, determination of KRAS status is recommended in mCRC patients before starting anti-EGFR therapies. Despite the application of these selective strategies, less than half of the chosen wild type KRAS patient population benefits from antiEGFR treatment [7,8,9].

Methods

Results

Discussion

Conclusion