J Cancer 2016; 7(15):2173-2178. doi:10.7150/jca.16551

Research Paper

To Excavate Biomarkers Predictive of the Response for Capecitabine plus RAD001 through Nanostring-Based Multigene Assay in Advanced Gastric Cancer Patients

Hansang Lee1, Jeeyun Lee1,2, Insuk Sohn3, Se Hoon Park1,2, Joon Oh Park1,2, Young Suk Park1,2, Kyoung-Mee Kim4, Won Ki Kang1,2, Seung Tae Kim1,2✉

1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;
2. Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;
3. Samsung Cancer Research Institute, Seoul, Korea;
4. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

Comprehensive characterization of individual patients' tumour is important to realize personalized medicine. Here, we investigate to identify subsets that benefit from capecitabine plus RAD001 in advanced gastric cancer (GC) patients by comprehensive high-throughput genomic analysis (nCounter assay). Archival tumour tissue blocks, if possible, were collected at phase II trial of capecitabine plus RAD001 in 47 refractory GC patients (at clinicaltrials.gov NCT#01099527). A total of 42 formalin-fixed, paraffin-embedded (FFPE) tumour samples were available for nanostring based-multigene Assay. An nCounter assay of 519 kinase panels has been used. We performed correlation analyses between expression levels of kinase genes and response for capecitabine plus RAD001. Among 42 patients with An nCounter assay of 519 kinase panels, 4 patients achieved confirmed partial response and 15 patients revealed stable disease, resulting in an overall response rate (ORR) of 9.5%. No difference in ORR was observed in terms of gender, performance status, primary tumour site, gastric resection, histologic subtype, Lauren classification, No. of metastatic site and No. of chemotherapy. In subgroups with response for capecitabine plus RAD001, there is significant overexpression of 6 genes among 519 kinase gene such as EPHA2 (P = 0.0025), PIM1 (P = 0.0031), KSR1 (P = 0.0033), and EIF2AK4 (P = 0.0046) that are related to the activation of mTOR signalling. This study is first report that investigated to identify biomarkers predictive of the response for RAD001 containing treatment in refractory GC patients, by comprehensive high-throughput genomic analysis (nCounter assay).

Keywords: Nanostring, RAD001, gastric cancer

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How to cite this article:
Lee H, Lee J, Sohn I, Park SH, Park JO, Park YS, Kim KM, Kang WK, Kim ST. To Excavate Biomarkers Predictive of the Response for Capecitabine plus RAD001 through Nanostring-Based Multigene Assay in Advanced Gastric Cancer Patients. J Cancer 2016; 7(15):2173-2178. doi:10.7150/jca.16551. Available from http://www.jcancer.org/v07p2173.htm