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APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency
10.1158/1535-7163.MCT-17-0834 2018-04-16 APTO-253 is a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. We sought to determine the mechanisms of action and basis for resistance to APTO-253 so as to identify synthetic lethal interacti... |
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Inhibition of the Histone H3K27 Demethylase UTX Enhances Tumor Cell Radiosensitivity
10.1158/1535-7163.MCT-17-1053 2018-04-13 The processes mediating the repair of DNA double-strand breaks (DSB) are critical determinants of radiosensitivity and provide a source of potential targets for tumor radiosensitization. Among the events required for efficient DSB repair are a variety of post... |
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Combined Inhibition of mTOR and CDK4/6 Is Required for Optimal Blockade of E2F Function and Long-term Growth Inhibition in Estrogen Receptor-positive Breast Cancer
10.1158/1535-7163.MCT-17-0537 2018-04-13 The cyclin dependent kinase (CDK)–retinoblastoma (RB)–E2F pathway plays a critical role in the control of cell cycle in estrogen receptor–positive (ER+) breast cancer. Small-molecule inhibitors of CDK4/6 have shown promise in this tumor type in combination wi... |
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EGF Receptor and mTORC1 are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors
10.1158/1535-7163.MCT-17-0137 2018-04-13 Germ cell tumors (GCT) are malignant tumors that arise from pluripotent embryonic germ cells and occur in children and young adults. GCTs are treated with cisplatin-based regimens which, while overall effective, fail to cure all patients and cause significant... |
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Impact of the Anticancer Drug NT157 on Tyrosine Kinase Signaling Networks
10.1158/1535-7163.MCT-17-0377 2018-04-13 The small-molecule drug NT157 has demonstrated promising efficacy in preclinical models of a number of different cancer types, reflecting activity against both cancer cells and the tumor microenvironment. Two known mechanisms of action are degradation of insu... |
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ABT-165, a Dual Variable Domain Immunoglobulin (DVD-Ig) Targeting DLL4 and VEGF, Demonstrates Superior Efficacy and Favorable Safety Profiles in Preclinical Models
10.1158/1535-7163.MCT-17-0800 2018-04-13 Antiangiogenic therapy is a clinically validated modality in cancer treatment. To date, all approved antiangiogenic drugs primarily inhibit the VEGF pathway. Delta-like ligand 4 (DLL4) has been identified as a potential drug target in VEGF-independent angioge... |
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Trastuzumab-Resistant HER2+ Breast Cancer Cells Retain Sensitivity to Poly (ADP-Ribose) Polymerase (PARP) Inhibition
10.1158/1535-7163.MCT-17-0302 2018-04-13 HER2-targeted therapies, such as trastuzumab, have increased the survival rates of HER2+ breast cancer patients. However, despite these therapies, many tumors eventually develop resistance to these therapies. Our lab previously reported an unexpected sensitiv... |
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A miR-29b Byproduct Sequence Exhibits Potent Tumor-Suppressive Activities via Inhibition of NF-{kappa}B Signaling in KRAS-Mutant Colon Cancer Cells
10.1158/1535-7163.MCT-17-0850 2018-04-13 We previously demonstrated that miR-29b-3p is a hopeful miRNA-based therapy against colorectal cancer. In this study, we aimed to clarify a value of miR-29b-1-5p as a next-generation treatment, especially for KRAS -mutant colorectal cancer. RT-PCR assay showe... |
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Targeting Polo-like Kinase 1 by a Novel Pyrrole-Imidazole Polyamide-Hoechst Conjugate Suppresses Tumor Growth In Vivo
10.1158/1535-7163.MCT-17-0747 2018-04-13 The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibit... |
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Cholesterol Depletion by TASIN-1 Induces Apoptotic Cell Death through the ER Stress/ROS/JNK Signaling in Colon Cancer Cells
10.1158/1535-7163.MCT-17-0887 2018-04-13 Truncated APC selective inhibitor-1 (TASIN-1) is a recently identified small molecule that selectively kills colorectal cancer cells that express truncated adenomatous polyposis coli (APC) by reducing cellular cholesterol levels. However, the downstream mecha... |