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dc.contributor.authorZulkifli, Ahmad Azri
dc.description© 2020 Ahmad Azri Zulkifli
dc.description.abstractColorectal cancer (CRC) is the fourth most common cancer diagnosed in Australia. Current standard treatment includes surgery, chemotherapy, and targeted therapy. Cetuximab is often used as part of the clinical management of unselected patients until a subset of patients were found to harbor KRAS mutations that conferred intrinsic resistance to Cetuximab. In addition, some patients are resistant to Cetuximab despite having wild-type KRAS. Using RNA-sequencing data and differential expression analysis, we discovered five potential biomarkers for predicting resistance to Cetuximab in CRC with wild-type KRAS. After generating 3 CRC models of acquired resistance to Cetuximab, we also employed proteomics analysis to determine potential biomarkers of acquired Cetuximab resistance in CRC cells with wild-type KRAS. In addition, we generated pre-clinical data for the repurposing of Carfilzomib (CFZ) as a novel drug to overcome Cetuximab resistance in metastatic colorectal cancer patients. In conclusion, this study provides a Cetuximab resistant model that can be used for further studies coupled with possible resistance mechanisms as well as a novel drug to overcome Cetuximab resistance.
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dc.subjectMetastatic colorectal cancer
dc.subjectEGFR-targeted therapy
dc.subjectCetuximab resistance
dc.subjectCarfilzomib treatment
dc.titleUnderstanding and overcoming resistance to epidermal growth factor receptor therapy
dc.typePhD thesis
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyMelbourne Medical School
melbourne.thesis.supervisornameRodney Luwor
melbourne.contributor.authorZulkifli, Ahmad Azri
melbourne.thesis.supervisorothernameStanley Stylli
melbourne.tes.fieldofresearch1310110 Receptors and membrane biology
melbourne.tes.fieldofresearch2310111 Signal transduction
melbourne.tes.fieldofresearch3321101 Cancer cell biology
melbourne.tes.fieldofresearch4321104 Cancer therapy (excl. chemotherapy and radiation therapy)
melbourne.accessrights This item is embargoed and will be available on 2022-11-24. This item is currently available to University of Melbourne staff and students only, login required.

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