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首页> 美国政府科技报告 >Chemotherapy of Late Stage Breast Cancer Targeted Towards Cell Cycle Regulatory Components
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Chemotherapy of Late Stage Breast Cancer Targeted Towards Cell Cycle Regulatory Components

机译：针对细胞周期调控成分的晚期乳腺癌化疗

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The original goal was to target cell cycle regulatory components as a potential therapy. The p16 gene is a tumor suppressor and a CDK inhibitor that is inactivated by gene methylation. The drug 5-aza-2'deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, was used for re-expression of a repressed p16. Although p16 re-activation occurred and cell growth was inhibited by 5-Aza-CdR, the effect was not specific to cells with a methylated p16 gene. A mouse model was developed and used to test the efficacy of 5-Aza-CdR. The results were not conclusive because of the inherent toxicity of 5-Aza-CdR. A blood test was developed for the detection of p16 methylation and used to show that the number of patients suitable for a 5- Aza-CdR clinical trial was very low (<3%). These results made a clinical trial with 5-Aza-CdR unrealistic. A phase II clinical trial with a second drug, Bryostatin-1, which regulates the p21 CDK inhibitor, was terminated due to dismal accrual rates even after initial success. Progress was made exploring the Cdc7 protein, which regulates the cell cycle and mutagenesis. Cdc7 may represent a new potential target as it was shown to be up- regulated in many breast cancer cell lines.

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