Correlation between MEK signature and Ras gene alteration in advanced gastric cancer

Oncotarget
Soomin AhnJeeyun Lee

Abstract

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.

References

Jun 14, 1991·Cancer Letters·H MikiT Enomoto
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Nov 8, 2005·Nature·David B SolitNeal Rosen
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Apr 27, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tanios Bekaii-SaabMiguel A Villalona-Calero
Jan 21, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Toshio ShimizuAmita Patnaik
Jun 8, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shunsuke Okumura, Pasi A Jänne
Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 26, 2014·Molecular Cancer Therapeutics·Shunsuke SogabeKazuto Nishio
Jan 24, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C A CarterG Giaccone

❮ Previous
Next ❯

Citations

Aug 31, 2020·The Journal of Applied Laboratory Medicine·Nicholas A VitanzaSarah E S Leary
Oct 22, 2019·Experimental Hematology & Oncology·Julie H SelimChung-Tsen Hsueh
Aug 9, 2020·Frontiers in Cell and Developmental Biology·Daipeng ZhouPeng Xu

❮ Previous
Next ❯

Methods Mentioned

BETA
RNAseq
Assay
PCR

Software Mentioned

nSolver Analysis
Nanostring
SPSS

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Roz BrantDarren R Hodgson
Nihon rinsho. Japanese journal of clinical medicine
Takunori UenoIchinosuke Hyodo
Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B
Viktoria S WarnekeChristoph Röcken
© 2022 Meta ULC. All rights reserved