Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the HER2/neu oncogene (also known as c-erbB2) is a frequent molecular event in multiple human cancers, including breast and ovarian cancer. Patients with cancer that overexpress HER2/neu are associated with unfavorable prognosis, shorter relapse time, and low survival rate. Treatments that target HER2/neu expression in cancer cells have been shown to be useful strategies to significantly reverse the malignancy induced by HER2/neu overexpression. The humanized anti-HER2/neu antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) has proven to be effective in clinical trials in patients with metastatic breast cancer. In addition, tyrosine kinase inhibitors such as emodin can also target the HER2/neu oncogenic activity. Emodin treatment inhibits HER2/neu tyrosine kinase activity and preferentially suppresses the transformation of HER2/neu-overexpressing breast cancer cells. Emodin also sensitizes HER2/neu-overexpressing cancer cells to chemotherapeutic agents, including cisplatin, doxorubicin, etoposide, and paclitaxel. Alternatively, HER2/neu overexpression can be repressed by attenuating the promoter activity of the HER2/neu gene. We have identified a number of potent transcriptional regulators, including the ets family member PEA3 and the adenovirus type 5 E1A, which are able to repress HER2/neu gene expression. Expression of these transcriptional regulators resulted in downregulation of HER2/neu promoter activity and reversed the transformed phenotype of the cancer cells in vitro. In vivo studies show that these HER2/neu repressors can act therapeutically as tumor suppressor genes for tumors that overexpress HER2/neu. These preclinical studies clearly indicate that transcriptional repressors that downregulate HER2/neu can be effective regimens for cancer treatment in a gene therapy format. More importantly, the tumor-free survival rate of treated animals is dramatically increased under nontoxic doses compared with untreated animals. A phase I clinical trial using E1A-liposome in breast and ovarian patients has recently been completed. Following treatment, we observed downregulation of the HER2/neu protein accompanied by E1A expression in both cancer and noncancer cells. Numbers of tumor cells in the pleural effusion or ascites were found to be dramatically reduced after treatment. Furthermore, apoptosis was strongly induced in the tumor cells. A phase II study has been started to further evaluate therapeutic efficacy and tumor suppression mechanisms of E1A. These studies show the clinical potential of targeting HER2/neu in cancer therapy.
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PMID:Targeting HER2: recent developments and future directions for breast cancer patients. 1177 2

Emodin (EMD) is an anthraquinone derivative extracted from the root and rhizome of Rheum palmatum L. which exhibits a range of activities, including anti-bacterial, antitumor, diuretic and vasorelaxant effects. The ability to inhibit metastasis and angiogenesis was shown in previous pharmacological studies, but clear information to address EMD affecting angiogenesis and metastasis in human breast cancer is still lacking. In the present study, we evaluated a possible role for EMD in angiogenesis and metastasis induced by breast cancer cells. It was revealed here that EMD attenuated tumor cell-induced metastasis and angiogenesis both in vitro and in vivo. Furthermore, it was found that these inhibitory effects were caused by MMPs and VEGFR-2 inhibition in metastatic breast cancer cells and endothelial cells, respectively. Western blot analysis showed reduction of Runx2 activation in the EMD-treated cells. ELISA based Runx2 transcription factor assay showed that the interaction between Runx2 and target sequences was inhibited by EMD. Our findings suggested that the inhibitory effects of EMD on tumor-induced metastasis and angiogenesis were caused by MMPs and VEGFR-2 inhibition, which may be associated with the downregulation of Runx2 transcriptional activity.
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PMID:The anthraquinone derivative Emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer. 2567 59