Please use this identifier to cite or link to this item:
https://doi.org/10.1158/1535-7163.MCT-15-0062
DC Field | Value | |
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dc.title | MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma | |
dc.contributor.author | Kong, Li Ren | |
dc.contributor.author | Chua, Kian Ngiap | |
dc.contributor.author | Sim, Wen Jing | |
dc.contributor.author | Ng, Hsien Chun | |
dc.contributor.author | Bi, Chonglei | |
dc.contributor.author | Ho, Jingshan | |
dc.contributor.author | Nga, Min En | |
dc.contributor.author | Pang, Yin Huei | |
dc.contributor.author | Ong, Weijie Richard | |
dc.contributor.author | Soo, Ross Andrew | |
dc.contributor.author | Huynh, The Hung | |
dc.contributor.author | Chng, Wee Joo | |
dc.contributor.author | Thiery, Jean-Paul | |
dc.contributor.author | Goh, Boon Cher | |
dc.date.accessioned | 2020-09-10T01:57:50Z | |
dc.date.available | 2020-09-10T01:57:50Z | |
dc.date.issued | 2015-07-01 | |
dc.identifier.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 | |
dc.identifier.issn | 15357163 | |
dc.identifier.issn | 15388514 | |
dc.identifier.uri | https://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.iso | en | |
dc.publisher | American Association for Cancer Research Inc. | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Oncology | |
dc.subject | PLATINUM-BASED CHEMOTHERAPY | |
dc.subject | RANDOMIZED PHASE-III | |
dc.subject | LUNG-CANCER | |
dc.subject | MELANOMA-CELLS | |
dc.subject | MUTATIONS | |
dc.subject | KINASE | |
dc.subject | GROWTH | |
dc.subject | HEAD | |
dc.subject | PROTEIN | |
dc.subject | GENE | |
dc.type | Article | |
dc.date.updated | 2020-09-09T22:33:45Z | |
dc.contributor.department | BIOMED INST FOR GLOBAL HEALTH RES & TECH | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | BIOCHEMISTRY | |
dc.contributor.department | MEDICINE | |
dc.contributor.department | PATHOLOGY | |
dc.contributor.department | PHARMACOLOGY | |
dc.description.doi | 10.1158/1535-7163.MCT-15-0062 | |
dc.description.sourcetitle | MOLECULAR CANCER THERAPEUTICS | |
dc.description.volume | 14 | |
dc.description.issue | 7 | |
dc.description.page | 1750-1760 | |
dc.description.place | United States | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS:MAPK Pathway Activation in Squamous Cell Carcinoma.pdf | 2.19 MB | Adobe PDF | OPEN | Published | View/Download |
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