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The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells.
(CELL PRESS, 2018-05-15)
Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration ...
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
(W B SAUNDERS CO-ELSEVIER INC, 2018-03-01)
BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ...
Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib.
(ELSEVIER SCIENCE BV, 2018-01-06)
UNLABELLED: Acquired drug resistance impacts the majority of patients being treated with tyrosine kinase inhibitors (TKIs) and remains a key challenge in modern anti-cancer therapy. The lack of clinically effective therapies ...
An In Vivo Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Chemotherapy remains the mainstay of treatment for advanced breast cancer; however, resistance is an inevitable event for the majority of patients with metastatic disease. Moreover, there is little information available ...
Src Is a Potential Therapeutic Target in Endocrine-Resistant Breast Cancer Exhibiting Low Estrogen Receptor-Mediated Transactivation.
(PUBLIC LIBRARY SCIENCE, 2016-06-16)
Despite the effectiveness of endocrine therapies in estrogen receptor positive (ER+) breast cancer, approximately 40% of patients relapse. Previously, we identified the Focal-adhesion kinase canonical pathway as a major ...
Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution.
(NATURE PUBLISHING GROUP, 2017-12-08)
Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not ...
Tumour kinome re-wiring governs resistance to palbociclib in oestrogen receptor positive breast cancers, highlighting new therapeutic modalities.
(SPRINGERNATURE, 2020-06-18)
Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than ...
Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness.
(NATURE PORTFOLIO, 2018-07-13)
Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) ...
A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors.
(NATURE PORTFOLIO, 2019-01-17)
Inhibition of the PARP superfamily tankyrase enzymes suppresses Wnt/β-catenin signalling in tumour cells. Here, we describe here a novel, drug-like small molecule inhibitor of tankyrase MSC2504877 that inhibits the growth ...