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  • Conoidin A mg The relationship of DDR expression to tumor ag

    2020-08-05

    The relationship of DDR1 Conoidin A mg to tumor aggressiveness or patient outcome has been investigated for other types of cancer, but these other investigations have typically only considered expression of tDDR1 protein. For example, Quan et al. reported that the DDR1 protein was highly expressed in 69% (46/67) of serous ovarian cancer tissue samples, and that its expression was correlated with pathologic grade of the tumor and clinical disease stage at the time of surgery. In colorectal cancer, Hu et al. found that increased DDR1 and decreased miR-199a-5p expression coexisted in colorectal cancer and suggested that upregulation of DDR1 induced by miR-199a-5p downregulation may contribute to activation of epithelial-mesenchymal transition and progression of colorectal cancer. Jian et al. found that DDR1 mRNA expression (by microarray analysis) was significantly higher in hepatocellular cancers with early recurrence compared with those without early recurrence using microarray technology and confirmed an association of evaluated DDR1 protein levels to early outcome using IHC. Immunohistochemical measurements of increased DDR1 protein in tumors have also been shown to correlate with poor survival for patients with bone metastasis in lung cancer, higher frequency of lymph node metastases in non–small cell lung cancer, and more frequent recurrences. Interestingly, ameloblastoma is generally classified as a benign neoplasm, and even in this situation, high expression of DDR1 protein correlates with aggressive clinical behavior. While these previous correlative studies have measured tDDR1 protein by IHC, these studies have not considered that pDDR1 could also be an important marker of cancer prognosis. A phosphoproteomic survey of lung cancer tissues did identify pDDR1 as one of the most commonly phosphorylated receptor kinases invasive lung cancer, but outcome data were not available for cases in this study. Not surprisingly, we found that all cases of ESCC with high levels of pDDR1 also showed high total expression of the protein, but even greater predictive value for poor outcome was seen in those cases with high pDDR1 as well as high tDDR1. Over the past decade, activation of specific protein kinases has been found to be effective targets cancer therapy, and a wide variety of inhibitors of protein kinases have been developed. DDR1 is one such kinase activated by collagen through phosphorylation, and several multikinase inhibitors, including imatinib, Conoidin A mg nilotinib, and dasatinib, inhibit DDR1 with similar potency.30, 31 Unfortunately, however, a number of clinical trials with these kinase inhibitors in the treatment of cancers that have activated DDR1 have been disappointing, possibly because the activity of this kinase is regulated not only by kinases, but rather by an intimate balance between kinases and antagonist phosphatases. Future strategies to target kinase activation might include kinase inhibitors in combination with agents that activate tumor suppressor phosphatase.