Molecular-targeting therapies against quantitative abnormalities in gene expression with malignant tumors

Abstract

Genetic mutations in exons of oncogenes and tumor-suppressor genes causing qualitative abnormalities result in activation of the oncogenes and inactivation of the tumor-suppressor genes, thereby causing cancer. In contrast, we have previously demonstrated that decreases in the RB promoter activity by genetic or epigenetic abnormalities can also cause carcinogenesis. In addition, activation and inactivation of a variety of oncogenes and tumor-suppressor genes finally cause quantitative abnormalities in gene expression. Interestingly, we discovered effective molecular-targeting agents, such as a novel MEK inhibitor, trametinib, by screening for agents upregulating the expression of cyclin-dependent kinase inhibitors. In the present review, we focused on the quantitative abnormalities in gene expression with carcinogenesis, and discuss the importance of normalizing the quantitative abnormalities in gene expression with several molecular-targeting agents.

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