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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 ...
A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.
(CELL PRESS, 2016-09-22)
The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the ...
Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells.
(NATURE PUBLISHING GROUP, 2018-08-01)
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome ...
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 ...
ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response.
(NATURE PORTFOLIO, 2020-02-01)
Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens to understand endocrine drug resistance, we discovered ARID1A and other SWI/SNF complex components as the factors most critically ...
BRCA1 and BRCA2 tumor suppressors protect against endogenous acetaldehyde toxicity.
(WILEY, 2017-10-01)
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source ...
Patient-derived tumour xenografts for breast cancer drug discovery.
(BIOSCIENTIFICA LTD, 2016-12-01)
Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market ...
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 ...
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 ...
The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation.
(BMC, 2020-06-01)
BACKGROUND: Limited studies examine the immune landscape in Esophageal Adenocarcinoma (EAC). We aim to identify novel associations, which may inform immunotherapy treatment stratification. METHODS: Three hundred twenty-nine ...