Please use this identifier to cite or link to this item: https://doi.org/10.1158/1535-7163.MCT-15-0062
Title: MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma
Authors: Kong, Li Ren 
Chua, Kian Ngiap 
Sim, Wen Jing 
Ng, Hsien Chun 
Bi, Chonglei
Ho, Jingshan 
Nga, Min En 
Pang, Yin Huei 
Ong, Weijie Richard
Soo, Ross Andrew 
Huynh, The Hung 
Chng, Wee Joo 
Thiery, Jean-Paul 
Goh, Boon Cher 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
PLATINUM-BASED CHEMOTHERAPY
RANDOMIZED PHASE-III
LUNG-CANCER
MELANOMA-CELLS
MUTATIONS
KINASE
GROWTH
HEAD
PROTEIN
GENE
Issue Date: 1-Jul-2015
Publisher: American Association for Cancer Research Inc.
Citation: Kong, Li Ren, Chua, Kian Ngiap, Sim, Wen Jing, Ng, Hsien Chun, Bi, Chonglei, Ho, Jingshan, Nga, Min En, Pang, Yin Huei, Ong, Weijie Richard, Soo, Ross Andrew, Huynh, The Hung, Chng, Wee Joo, Thiery, Jean-Paul, Goh, Boon Cher (2015-07-01). MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma. MOLECULAR CANCER THERAPEUTICS 14 (7) : 1750-1760. ScholarBank@NUS Repository. https://doi.org/10.1158/1535-7163.MCT-15-0062
Abstract: © 2015 American Association for Cancer Research. Genomic analyses of squamous cell carcinoma (SCC) have yet to yield significant strategies against pathway activation to improve treatment. Platinum-based chemotherapy remains the mainstay of treatment for SCC of different histotypes either as a single-agent or alongside other chemotherapeutic drugs or radiotherapy; however, resistance inevitably emerges, which limits the duration of treatment response. To elucidate mechanisms that mediate resistance to cisplatin, we compared drug-induced perturbations to gene and protein expression between cisplatinsensitive and -resistant SCC cells, and identified MAPK-ERK pathway upregulation and activation in drug-resistant cells. ERK-induced resistance appeared to be activated by Son of Sevenless (SOS) upstream, and mediated through Bim degradation downstream. Clinically, elevated p-ERK expression was associated with shorter disease-free survival in patients with locally advanced head and neck SCC treated with concurrent chemoradiation. Inhibition of MEK/ERK, but not that of EGFR or RAF, augmented cisplatin sensitivity in vitro and demonstrated efficacy and tolerability in vivo. Collectively, these findings suggest that inhibition of the activated SOS-MAPK-ERK pathway may augment patient responses to cisplatin treatment.
Source Title: MOLECULAR CANCER THERAPEUTICS
URI: https://scholarbank.nus.edu.sg/handle/10635/175514
ISSN: 15357163
15388514
DOI: 10.1158/1535-7163.MCT-15-0062
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS:MAPK Pathway Activation in Squamous Cell Carcinoma.pdf2.19 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

33
checked on Apr 7, 2021

Page view(s)

71
checked on Apr 9, 2021

Download(s)

1
checked on Apr 9, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.