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Mechanism of Sorafenib Resistance in Patients With Advanced Hepatocellular Carcinoma
It has been shown previously that gene expression profiling signature (a set of dysregulated genes) can be used for molecular classification, diagnosis, and prognosis of several types of cancers. In This study the hypothesise that resistant tumor may be due to genetic mutations and/or other alternative pathways that could be the reason to overcome the Sorafenib and still proliferate. Primary objectives To evaluate the primary and secondary potential mechanisms by which HCC patients on Sorafenib treatment would be resistant to therapy and also identify the favorable genetic makeup of patients responding to treatment. Measures of primary outcome: * cDNA microarray analysis on the MAP kinase pathway. * mRNA quantification of genetic expression (RT-PCR) for identification of upregulated genes, and confirmed by corresponding proteomic testing (by Mass Spectroscopy) in the serum for potential serum markers. Secondary Objectives Progression free survival: Time to disease progression in patients in Saudi Arabia with HCC receiving Sorafenib: \[defined as time, in weeks, from the baseline visit to progression of the disease or death from any cause\] will be diagnosed using the RECIST criteria based on a trimestrial abdominal CT evaluation. * Survival rates and Predictors of survival: * Survival defined as the time from baseline visit to death from any cause \[in weeks\]. * Variables identified in multivariate regression analysis from overall treated patients independently associated with survival till study completion or death. Justification and Value to the Kingdom Sorafenib in the treatment of advanced HCC is a recent development. Since the only current effective treatment for advanced HCC is resection or transplantation and the list for these procedures are ever-growing due to the confounding effect of the lack of infrastructure in the Kingdom, selecting treatment for patients who are more likely to respond to Sorafenib treatment The Long-Term Comprehensive Nationa
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