Recent submissions
Now showing items 301-320 of 889
-
Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.
(CELL PRESS, 2018-01-30)Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically ... -
CancerGD: a resource for identifying and interpreting genetic dependencies in cancer
(2016-10-26)Abstract Genes whose function is selectively essential in the presence of cancer associated genetic aberrations represent promising targets for the development of precision therapeutics. Here we present CancerGD ( ... -
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as BRCA2 HRR defects confer synthetic lethality to PARP inhibitors (PARPi) ... -
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 ... -
Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-08-05)Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to ... -
Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance.
(AMER ASSOC CANCER RESEARCH, 2020-10-01)Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This ... -
Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours.
(BMJ PUBLISHING GROUP, 2020-09-03)OBJECTIVE: A comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to identify ... -
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.
(ELSEVIER, 2020-09-01)BACKGROUND: In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. ... -
Critical Appraisal of Programmed Death Ligand 1 Reflex Diagnostic Testing: Current Standards and Future Opportunities.
(ELSEVIER SCIENCE INC, 2019-01-01)INTRODUCTION: Patient suitability to anti-programmed death ligand 1 (PD-L1) immune checkpoint inhibition is key to the treatment of NSCLC. We present, applied to PD-L1 testing: a comprehensive cross-validation of two ... -
Chlorambucil targets BRCA1/2-deficient tumours and counteracts PARP inhibitor resistance.
(WILEY, 2019-07-01)Due to compromised homologous recombination (HR) repair, BRCA1- and BRCA2-mutated tumours accumulate DNA damage and genomic rearrangements conducive of tumour progression. To identify drugs that target specifically ... -
Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach.
(SPRINGERNATURE, 2019-04-16)BACKGROUND: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 ... -
A Machine Learning Platform to Optimize the Translation of Personalized Network Models to the Clinic.
(AMER SOC CLINICAL ONCOLOGY, 2019-04-17)PURPOSE: Dynamic network models predict clinical prognosis and inform therapeutic intervention by elucidating disease-driven aberrations at the systems level. However, the personalization of model predictions requires the ... -
Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma.
(BMJ PUBLISHING GROUP, 2019-11-01)OBJECTIVE: Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following ... -
NUQA: Estimating Cancer Spatial and Temporal Heterogeneity and Evolution through Alignment-Free Methods.
(OXFORD UNIV PRESS, 2019-12-01)Longitudinal next-generation sequencing of cancer patient samples has enhanced our understanding of the evolution and progression of various cancers. As a result, and due to our increasing knowledge of heterogeneity, such ... -
Systematic evaluation of PAXgene® tissue fixation for the histopathological and molecular study of lung cancer.
(WILEY, 2019-11-11)Whilst adequate for most existing pathological tests, formalin is generally considered a poor DNA preservative and use of alternative fixatives may prove advantageous for molecular testing of tumour material; an increasingly ... -
Development of a cell-free split-luciferase biochemical assay as a tool for screening for inhibitors of challenging protein-protein interaction targets.
(F1000 Research Ltd, 2020-01-01)Targeting the interaction of proteins with weak binding affinities or low solubility represents a particular challenge for drug screening. The NanoLuc â ® Binary Technology (NanoBiT â ®) was originally developed to detect ... -
Digital pathology and artificial intelligence will be key to supporting clinical and academic cellular pathology through COVID-19 and future crises: the PathLAKE consortium perspective.
(BMJ PUBLISHING GROUP, 2020-07-03)The measures to control the COVID-19 outbreak will likely remain a feature of our working lives until a suitable vaccine or treatment is found. The pandemic has had a substantial impact on clinical services, including ... -
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 ... -
Comparison of a coaxial versus non-coaxial liver biopsy technique in an oncological setting: diagnostic yield, complications and seeding risk.
(SPRINGER, 2020-07-14)OBJECTIVES: Percutaneous liver biopsy (PLB) poses specific challenges in oncological patients such as bleeding and tumour seeding. This study's aim was to compare a coaxial (C-PLB) and non-coaxial (NC-PLB) biopsy technique ...