Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy resistance in ovarian cancer remains an unsolved problem in caring for women with this disease. We now show that ovarian cancer immunoreactive antigen domain containing 1 (OCIAD1) has higher expression in chemoresistant compared with chemosensitive ovarian cancer cell lines. We have designed a novel secondary cell homing assay (SCHA) to test the ability of cells to withstand chemotherapy and form secondary colonies that could form recurrent disease. OCIAD1 upregulated cells had significantly higher secondary colony-forming ability than had OCIAD1 downregulated cells following treatment with paclitaxel. Additionally, 18:1 lysophosphatidic acid (LPA) increases OCIAD1 expression in a time- and dose-dependent manner. LPA stimulates OCIAD1 serine phosphorylation within two hours of stimulation. Transfection of MKK6 increases OCIAD1 expression but nuclear translocation is inhibited. Inhibition of p38 mitogen-activated protein kinase blocks LPA-induced OCIAD1 expression. Cycloheximide treatment of MKK6-transfected cells does not inhibit OCIAD1 expression, suggesting that MKK6 upregulation is not translationally controlled. OCIAD1 downregulation knocks down LPA-induced cell adhesion to collagen I and laminin 10/11 and specifically inhibits cell attachment to alpha2, alpha5, alphaV, and beta1 integrins. Proteomic studies indicate that OCIAD1 is physically attached to alpha actin 4 and beta actin. Thus, OCIAD1 may play a role in cytoskeletal function which can alter sensitivity to paclitaxel. This is the first study to indicate that OCIAD1 is a key player in generating ovarian cancer recurrence; it is functionally controlled by LPA and MKK6 signaling, and inhibition of OCIAD1 could be an important strategy in the management of recurrent ovarian cancer.
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PMID:Role of the 18:1 lysophosphatidic acid-ovarian cancer immunoreactive antigen domain containing 1 (OCIAD1)-integrin axis in generating late-stage ovarian cancer. 2051 46

Traditional treatment failure in recurrent ovarian cancer remains a challenge for clinicians. Tumor genetic testing is a promising tool which has been proved able to identify sensitivity profiles in patients affected by cancers. This may be helpful in choosing targeted systemic treatments, aiming to overcome histology boundaries and to avoid unnecessary toxicity. We describe the case of a patient affected by recurrent high-grade serous ovarian cancer responsive to MEK-inhibitors, who had undergone multiple lines of therapy. To our knowledge, this is the first reported case of recurrent high-grade ovarian cancer showing remarkable clinical, radiologic and biochemical response to trametinib. This report suggests that trametinib could be effective in high-grade serous ovarian cancer, although most of promising scientific data on this molecule have focused on low-grade ovarian cancer. Molecular profiling has gradually become part of care for patients affected by recurrent ovarian cancer, however further randomized studies are needed to prove its efficacy in everyday clinical practice.
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PMID:Trametinib response in heavily pretreated high-grade ovarian cancer: One step towards precision medicine. 3212 57