Correlation between MEK signature and Ras gene alteration in advanced gastric cancer
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Soomin Ahn1,*, Roz Brant2,*, Alan Sharpe3, Jonathan R. Dry4, Darren R. Hodgson2, Elaine Kilgour2, Kyung Kim5, Seung Tae Kim5, Se Hoon Park5, Won Ki Kang5, Kyoung-Mee Kim1 and Jeeyun Lee5
1Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2AstraZeneca, Oncology Innovative Medicines, Alderley Park, Macclesfield, UK
3AstraZeneca, Cambridge, UK
4AstraZeneca, Boston, Massachusetts, USA
5Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
*These authors contributed equally to this work
Jeeyun Lee, email: firstname.lastname@example.org
Keywords: gastric cancer, KRAS, MEK, selumetinib
Received: December 27, 2016 Accepted: May 05, 2017 Published: May 23, 2017
MEK inhibitor (selumetinib) is a potent, orally active inhibitor of MAPK/ERK pathway. It is important to develop an accurate and robust method indicative of RAS pathway activity to stratify potential patients who can benefit from selumetinib treatment in gastric cancer (GC). First, we surveyed the sensitivity to selumetinib in a panel of 22 GC cell lines and correlated with MEK signature to selumetinib sensitivity. Next, we analyzed MEK signature via nanostring assay in two Asian cohorts using clinical samples (n = 218) and then performed a correlative analysis with MEK signature status and KRAS genotype in GC. MEK signature was predictive of response of selumetinib in GC cell lines regardless of KRAS mutation status. The proportion of high MEK signature by nanostring assay was 6.9% and the proportion of high MEK signature was significantly higher in KRAS altered group in a Korean cohort. None of PIK3CA altered cases belonged to high MEK signature group. MEK high signature was more prevalent in intestinal type by Lauren classification. The correlation between MEK signature, KRAS alteration and treatment response to selumetinib should be validated in prospective clinical trials.
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