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Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors.
(ELSEVIER, 2020-11-08)
BACKGROUND: Deleterious ATM alterations are found in metastatic prostate cancer (PC); PARP inhibition has antitumour activity against this subset, but only some ATM loss PCs respond. OBJECTIVE: To characterise ATM-deficient ...
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 ...
Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival.
(ROCKEFELLER UNIV PRESS, 2019-11-04)
In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival ...
Clonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme.
(ELSEVIER SCI LTD, 2019-11-01)
INTRODUCTION: The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced ...
Longitudinal analysis of a secondary BRCA2 mutation using digital droplet PCR.
(WILEY, 2019-11-20)
Development of resistance to platinum and poly(ADP-ribose) polymerase inhibitors via secondary BRCA gene mutations that restore functional homologous recombination has been observed in a number of cancer types. Here we ...
A decade of clinical development of PARP inhibitors in perspective.
(ELSEVIER, 2019-09-01)
Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce ...
Beyond DNA repair: the novel immunological potential of PARP inhibitors.
(TAYLOR & FRANCIS INC, 2019-01-01)
Loss of excision repair cross-complementation group 1 (ERCC1), frequently found in lung cancer, and mutations in breast cancer type 1/2 susceptibility genes (BRCA1/2), often found in ovarian, breast and prostate cancers, ...
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 ...
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A.
(NATURE PUBLISHING GROUP, 2016-12-13)
Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ...
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) ...