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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 ...
Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy.
(BMJ PUBLISHING GROUP, 2020-01-01)
Patients with cancer who developed severe, grade 3 or 4 immune-related adverse events (irAEs) during therapy with immune checkpoint inhibitors are at risk for developing severe toxicities again on rechallenge with checkpoint ...
Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations.
(ELSEVIER, 2023-03-01)
BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only ...
Genome-Protective Topoisomerase 2a-Dependent G2 Arrest Requires p53 in hTERT-Positive Cancer Cells.
(American Association for Cancer Research (AACR), 2022-05-03)
UNLABELLED: Topoisomerase 2a (Topo2a)-dependent G2 arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this arrest is dysfunctional, a PKCε-dependent failsafe pathway can be ...
Tissue architecture in tumor initiation and progression.
(CELL PRESS, 2022-06-01)
The 3D architecture of tissues bearing tumors impacts on the mechanical microenvironment of cancer, the accessibility of stromal cells, and the routes of invasion. A myriad of intrinsic and extrinsic forces exerted by the ...
Half of germline pathogenic and likely pathogenic variants found on panel tests do not fulfil NHS testing criteria.
(NATURE PORTFOLIO, 2022-02-21)
Genetic testing for cancer predisposition has been curtailed by the cost of sequencing, and testing has been restricted by eligibility criteria. As the cost of sequencing decreases, the question of expanding multi-gene ...
Hallmarks of Resistance to Immune-Checkpoint Inhibitors.
(AMER ASSOC CANCER RESEARCH, 2022-04-01)
Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs ...
A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma.
(SPRINGERNATURE, 2023-09-21)
BACKGROUND: The first-in-class brain-penetrating synthetic hydroxylated lipid idroxioleic acid (2-OHOA; sodium 2-hydroxyoleate), activates sphingomyelin synthase expression and regulates membrane-lipid composition and ...
A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.
(SPRINGERNATURE, 2023-09-01)
Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, ...
Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.
(BMC, 2018-05-31)
BACKGROUND: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic ...