Please use this identifier to cite or link to this item: https://doi.org/10.1158/1535-7163.MCT-15-0062
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dc.titleMEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma
dc.contributor.authorKong, Li Ren
dc.contributor.authorChua, Kian Ngiap
dc.contributor.authorSim, Wen Jing
dc.contributor.authorNg, Hsien Chun
dc.contributor.authorBi, Chonglei
dc.contributor.authorHo, Jingshan
dc.contributor.authorNga, Min En
dc.contributor.authorPang, Yin Huei
dc.contributor.authorOng, Weijie Richard
dc.contributor.authorSoo, Ross Andrew
dc.contributor.authorHuynh, The Hung
dc.contributor.authorChng, Wee Joo
dc.contributor.authorThiery, Jean-Paul
dc.contributor.authorGoh, Boon Cher
dc.date.accessioned2020-09-10T01:57:50Z
dc.date.available2020-09-10T01:57:50Z
dc.date.issued2015-07-01
dc.identifier.citationKong, 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
dc.identifier.issn15357163
dc.identifier.issn15388514
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175514
dc.description.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.
dc.language.isoen
dc.publisherAmerican Association for Cancer Research Inc.
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectPLATINUM-BASED CHEMOTHERAPY
dc.subjectRANDOMIZED PHASE-III
dc.subjectLUNG-CANCER
dc.subjectMELANOMA-CELLS
dc.subjectMUTATIONS
dc.subjectKINASE
dc.subjectGROWTH
dc.subjectHEAD
dc.subjectPROTEIN
dc.subjectGENE
dc.typeArticle
dc.date.updated2020-09-09T22:33:45Z
dc.contributor.departmentBIOMED INST FOR GLOBAL HEALTH RES & TECH
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentBIOCHEMISTRY
dc.contributor.departmentMEDICINE
dc.contributor.departmentPATHOLOGY
dc.contributor.departmentPHARMACOLOGY
dc.description.doi10.1158/1535-7163.MCT-15-0062
dc.description.sourcetitleMOLECULAR CANCER THERAPEUTICS
dc.description.volume14
dc.description.issue7
dc.description.page1750-1760
dc.description.placeUnited States
dc.published.statePublished
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