Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/124088
Title: INVESTIGATION OF RAS-DEPENDENT GENE EXPRESSION & CELL SURVIVAL SIGNALLING IN COLORECTAL CANCER
Authors: PEK MI XUE MICHELLE
Keywords: Colorectal cancer, KRAS, KRAS dependency, MEK, CDK4/6, FOXM1
Issue Date: 11-Jan-2016
Source: PEK MI XUE MICHELLE (2016-01-11). INVESTIGATION OF RAS-DEPENDENT GENE EXPRESSION & CELL SURVIVAL SIGNALLING IN COLORECTAL CANCER. ScholarBank@NUS Repository.
Abstract: KRAS MUTATION OCCURS IN UP TO 60% OF COLORECTAL CANCERS (CRC) AND DEVELOPMENT OF EFFECTIVE TARGETED THERAPIES STILL REMAINS A CHALLENGE. STUDIES HAVE HIGHLIGHTED THE ISSUE OF KRAS DEPENDENCY AND INDEPENDENCY, IMPLYING THAT KRAS MUTATION STATUS IS INADEQUATE AS A BIOMARKER OF TREATMENT RESPONSE. THROUGH INTEGRATION OF QUANTITATIVE KRAS MUTATION PYROSEQUENCING DATA AND GENE EXPRESSION PROFILING IN CRC TUMORS, WE DEFINE A KRAS DEPENDENCY GENE SIGNATURE WHICH EXHIBITS ENRICHMENT IN CELL CYCLE AND MITOTIC PROCESSES, TOGETHER WITH ELEVATED FOXM1 EXPRESSION. WE PROPOSED A THERAPEUTIC STRATEGY USING CDK4/6 AND MEK INHIBITORS THAT TARGETS KRAS-DRIVEN MOLECULAR SIGNATURE AND REDUCES VIABILITY OF KRAS-DEPENDENT AND BRAF-MUTANT CRC VIA SYNERGISTIC DEPLETION OF FOXM1 AND REDUCTION OF OTHER MITOTIC TRANSCRIPTION FACTORS, BOTH IN VITRO AND IN VIVO OUR STUDY THUS ESTABLISHES KRAS DEPENDENCY GENE SIGNATURE AS A POTENTIAL BIOMARKER OF RESPONSE AND COMBINATORIAL INHIBITION OF CDK4/6 AND MEK AS A PROMISIN
URI: http://scholarbank.nus.edu.sg/handle/10635/124088
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