Novel Combination Therapy: Monensin Potentiates Erlotinib-Induced Cytotoxicity

FieldValue
dc.contributor.authorKhalil, Dayekh
dc.date.accessioned2013-08-19T18:44:12Z
dc.date.available2013-08-19T18:44:12Z
dc.date.created2013
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/10393/24405
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-3164
dc.description.abstractReceptor Tyrosine Kinase (RTK) inhibitors, such as erlotinib/tarceva, have been introduced in the past decade as a promising therapeutic option in Head and Neck Squamous Cell Carcinoma (HNSCC), however, they lack significant efficacy as single agents. As a result, RTK inhibitors require a combination based therapeutic approach with other treatment modalities. To uncover such a combination of agents, we performed a high throughput Prestwick library screen that included 1200 compounds approved by the FDA on HNSCC cell lines and found that monensin, a coccidial antibiotic, synergistically enhanced the cytotoxicity of erlotinib. RT-PCR revealed that monensin induced the expression of Activation of Transcription Factor (ATF) 3 and its downstream target C/EBP homologous protein (CHOP) which are key regulators of apoptosis. Furthermore, RNA-Seq analysis suggests that monensin augments erlotinib cytotoxicity by disturbing lipid and sterol biosynthesis. Therefore, identifying the mechanism of action exerted by monensin may open alternative avenues of cancer treatment.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectmonensin
dc.subjecterlotinib
dc.subjectlovastatin
dc.subjecthead and neck squamous cell carcinoma
dc.subjectcombination treatment
dc.titleNovel Combination Therapy: Monensin Potentiates Erlotinib-Induced Cytotoxicity
dc.typeThesis
dc.faculty.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
dc.contributor.supervisorDimitroulakos, Jim
dc.embargo.termsimmediate
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
CollectionThèses, 2011 - // Theses, 2011 -

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