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https://www.selleckchem.com/ Novel therapeutic strategies are urgently required for the clinical management of chemoresistant ovarian carcinoma, which is the most lethal of the gynecological malignancies. MicroRNAs (miRNAs) hold promise because they play a critical role in determining the cell phenotype by regulating several hundreds of targets, which could constitute vulnerabilities of cancer cells. A combination of gain of function miRNA screening and real-time continuous cell monitoring allows the identification of miRNAs with robust cytotoxic effects in chemoresistant ovarian cancer cells. Focusing on miR-3622b-5p, we show that it induces apoptosis in several ovarian cancer cell lines by both directly targeting Bcl-xL and EGFR mediating BIM upregulation. MiR-3622b-5p also sensitizes cells to cisplatin by inhibiting Bcl-xL in ovarian cancer cell lines escaping BIM induction. MiR-3622b-5p also exerts anti migratory capacities by targeting both LIMK1 and NOTCH1. These wide ranging antitumor properties of miR-3622b-5p in ovarian cancer cells are mimicked by the associations of pharmacological inhibitors targeting these proteins. The combination of an EGFR inhibitor together with a BH3-mimetic molecule induced a large decrease in cell viability in a panel of ovarian cancer cell lines and several ovarian patient derived tumor organoids, suggesting the value of pursuing such a combination therapy in ovarian carcinoma. Altogether, our work highlights the potential of phenotype based miRNA screening approaches to identify lethal interactions which might lead to new drug combinations and clinically applicable strategies. Copyright ©2020, American Association for Cancer Research.Tumor-associated M2-macrophages are one of the most abundant immunosuppressive cell types in the PDAC TME. However, the molecular mechanisms responsible for the generation of M2-macrophages are unclear. Here we demonstrated that overexpression of DCLK1-isoform2 in AsPC1 and MIA PaCa2 cells resulted

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