Recent submissions
Now showing items 421-440 of 658
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Loss of heterozygosity as a marker of homologous repair deficiency in multiple myeloma: a role for PARP inhibition?
(NATURE PUBLISHING GROUP, 2018-07-01)PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a ... -
Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.
(WILEY, 2017-12-01)UNLABELLED: The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully ... -
Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial.
(ELSEVIER SCIENCE INC, 2018-08-01)BACKGROUND: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug ... -
Privileged Structures and Polypharmacology within and between Protein Families.
(AMER CHEMICAL SOC, 2018-12-13)Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ... -
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
(ELSEVIER, 2018-09-25)Despite the recent progress in treatment of multiple myeloma (MM), it is still an incurable malignant disease, and we are therefore in need of new risk stratification tools that can help us to understand the disease and ... -
Detection of circulating tumour cell clusters in human glioblastoma.
(NATURE PUBLISHING GROUP, 2018-08-14)Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular ... -
RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2019-01-15)PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic ... -
Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS.
(AMER CHEMICAL SOC, 2018-09-13)Proteins in the RAS family are important regulators of cellular signaling and, when mutated, can drive cancer pathogenesis. Despite considerable effort over the last 30 years, RAS proteins have proven to be recalcitrant ... -
To Cycle or Fight-CDK4/6 Inhibitors at the Crossroads of Anticancer Immunity.
(2019-01)Dysregulation of cell division resulting in aberrant cell proliferation is a key hallmark of cancer, making it a rational and important target for innovative anticancer drug development. Three selective cyclin-dependent ... -
Driving next-generation autophagy researchers towards translation (DRIVE), an international PhD training program on autophagy.
(TAYLOR & FRANCIS INC, 2019-02-01)The European autophagy consortium Driving next-generation autophagy researchers towards translation (DRIVE) held its kick-off meeting in Groningen on the 14th and 15th of June 2018. This Marie Skłodowska-Curie Early Training ... -
Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models.
(SOC NUCLEAR MEDICINE INC, 2019-03-01)In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR monoclonal ... -
Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre.
(2018-10-15)Background Greater understanding of the molecular classification of breast cancer has permitted the development of rational drug design strategies. In a phase I clinical trial setting, molecular profiling with next-generation ... -
A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials.
(ELSEVIER SCI LTD, 2018-11-01)BACKGROUND: The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according ... -
SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.
(AMER ASSOC CANCER RESEARCH, 2018-11-15)Purpose: CHD1 deletions and SPOP mutations frequently cooccur in prostate cancer with lower frequencies reported in castration-resistant prostate cancer (CRPC). We monitored CHD1 expression during disease progression and ... -
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
(NATURE PUBLISHING GROUP, 2019-03-07)Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ... -
Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates.
(AMER CHEMICAL SOC, 2018-09-21)APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate ... -
Combining Mutational Signatures, Clonal Fitness, and Drug Affinity to Define Drug-Specific Resistance Mutations in Cancer.
(CELL PRESS, 2018-11-15)The emergence of mutations that confer resistance to molecularly targeted therapeutics is dependent upon the effect of each mutation on drug affinity for the target protein, the clonal fitness of cells harboring the mutation, ... -
Leveraging Human Genetics to Guide Cancer Drug Development.
(AMER SOC CLINICAL ONCOLOGY, 2018-11-21)PURPOSE: The high attrition rate of cancer drug development programs is a barrier to realizing the promise of precision oncology. We have examined whether the genetic insights from genome-wide association studies of cancer ... -
Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma.
(NATURE PUBLISHING GROUP, 2018-10-30)BACKGROUND: AKT is commonly overexpressed in tumours and plays an important role in the metabolic reprogramming of cancer. We have used magnetic resonance spectroscopy (MRS) to assess whether inhibition of AKT signalling ... -
MoKCa database--mutations of kinases in cancer.
(OXFORD UNIV PRESS, 2009-01-01)Members of the protein kinase family are amongst the most commonly mutated genes in human cancer, and both mutated and activated protein kinases have proved to be tractable targets for the development of new anticancer ...