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A Machine-Learning Tool Concurrently Models Single Omics and Phenome Data for Functional Subtyping and Personalized Cancer Medicine.
(MDPI, 2020-09-30)
One of the major challenges in defining clinically-relevant and less heterogeneous tumor subtypes is assigning biological and/or clinical interpretations to etiological (intrinsic) subtypes. Conventional clustering/subtyping ...
Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD.
(CELL PRESS, 2021-02-18)
Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair ...
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial.
(AMER ASSOC CANCER RESEARCH, 2021-11-01)
PARP inhibitors are approved for treating advanced prostate cancers (APC) with various defective DNA repair genes; however, further studies to clinically qualify predictive biomarkers are warranted. Herein we analyzed ...
The Mutational Concordance of Fixed Formalin Paraffin Embedded and Fresh Frozen Gastro-Oesophageal Tumours Using Whole Exome Sequencing.
(MDPI, 2021-01-09)
UNLABELLED: 1. BACKGROUND: The application of massively parallel sequencing has led to the identification of aberrant druggable pathways and somatic mutations within therapeutically relevant genes in gastro-oesophageal ...
HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.
(CELL PRESS, 2020-05-12)
Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic ...
Opinion: PARP inhibitors in cancer-what do we still need to know?
(The Royal Society, 2022-07-01)
PARP inhibitors (PARPi) have been demonstrated to exhibit profound anti-tumour activity in individuals whose cancers have a defect in the homologous recombination DNA repair pathway. Here, we describe the current consensus ...
Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma.
(MDPI, 2021-07-30)
Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function ARID1A mutations and a poor response to chemotherapy. Despite their generally low ...
Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency.
(NATURE PORTFOLIO, 2021-11-08)
PARP enzymes utilise NAD+ as a co-substrate for their enzymatic activity. Inhibition of PARP1 is synthetic lethal with defects in either BRCA1 or BRCA2. In order to assess whether other genes implicated in NAD+ metabolism ...
European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer.
(ELSEVIER, 2022-03-01)
BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers ...
Resistance to DNA repair inhibitors in cancer.
(WILEY, 2022-05-14)
The DNA damage response (DDR) represents a complex network of proteins which detect and repair DNA damage, thereby maintaining the integrity of the genome and preventing the transmission of mutations and rearranged chromosomes ...