Browsing Cancer Therapeutics by title
Now showing items 451-470 of 657
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Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci
(2018-01-01)Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites ... -
Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo.
(SPRINGER, 2020-07-01)PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) ... -
Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial.
(ELSEVIER SCIENCE INC, 2020-01-01)BACKGROUND: Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and ... -
On the origins of three-dimensionality in drug-like molecules.
(2016-09)Aim Many medicinal chemistry-relevant structures and core scaffolds tend toward geometric planarity, which hampers the optimization of physicochemical properties desirable in drug-like molecules. As challenging drug target ... -
Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling.
(ELSEVIER SCIENCE INC, 2018-04-01)Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. ... -
Oncolytic Herpes Simplex Virus Inhibits Pediatric Brain Tumor Migration and Invasion.
(CELL PRESS, 2017-06-16)Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via ... -
Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer.
(NATURE PUBLISHING GROUP, 2016-04-01)Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy ... -
Optimising the value of immunomodulatory drugs during induction and maintenance in transplant ineligible patients with newly diagnosed multiple myeloma: results from Myeloma XI, a multicentre, open-label, randomised, Phase III trial.
(WILEY, 2021-03-01)Second-generation immunomodulatory agents, such as lenalidomide, have a more favourable side-effect profile than the first-generation thalidomide, but their optimum combination and duration for patients with newly diagnosed ... -
Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors.
(AMER CHEMICAL SOC, 2022-06-23)To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on ... -
Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial.
(AMER SOC HEMATOLOGY, 2023-04-06)Prediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in ... -
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
(AMER SOC CLINICAL INVESTIGATION INC, 2020-11-02)The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ... -
Over-expression of the miR-483-3p overcomes the miR-145/TP53 pro-apoptotic loop in hepatocellular carcinoma.
(IMPACT JOURNALS LLC, 2016-05-24)The miR-145-5p, which induces TP53-dependent apoptosis, is down-regulated in several tumors, including hepatocellular carcinomas (HCCs), but some HCCs show physiological expression of this miR. Here we demonstrate that in ... -
Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma (MM)
(OAE PUBLISHING INC, 2022-01-01)<jats:p>Malignant mesothelioma (MM) is a rare, aggressive solid tumor with limited therapeutic options and poor therapeutic response. The role of immunotherapy in MM is now well established and therapeutic options, such ... -
Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.
(SPRINGERNATURE, 2017-03-31)Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly ... -
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
(AMER ASSOC CANCER RESEARCH, 2016-09-29)Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ... -
Pan RAS-binding compounds selected from a chemical library by inhibiting interaction between RAS and a reduced affinity intracellular antibody.
(NATURE PORTFOLIO, 2021-01-18)Intracellular antibodies are valuable tools for target validation studies for clinical situations such as cancer. Recently we have shown that antibodies can be used for drug discovery in screening for chemical compounds ... -
A pan-cancer analysis of the frequency of DNA alterations across cell cycle activity levels.
(SPRINGERNATURE, 2020-08-06)Pan-cancer genomic analyses based on the magnitude of pathway activity are currently lacking. Focusing on the cell cycle, we examined the DNA mutations and chromosome arm-level aneuploidy within tumours with low, intermediate ... -
Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma.
(CELL PRESS, 2015-01-12)BRAF and MEK inhibitors are effective in BRAF mutant melanoma, but most patients eventually relapse with acquired resistance, and others present intrinsic resistance to these drugs. Resistance is often mediated by pathway ... -
PARP Inhibitors for Advanced Prostate Cancer: Validating Predictive Biomarkers.
(ELSEVIER, 2019-10-01) -
Pathogenic ACVR1R206H activation by Activin A-induced receptor clustering and autophosphorylation.
(WILEY, 2021-07-15)Fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) are debilitating diseases that share causal mutations in ACVR1, a TGF-β family type I receptor. ACVR1R206H is a frequent mutation in ...