Targeting DNA damage response pathways in cancer

FJ Groelly, M Fawkes, RA Dagg, AN Blackford… - Nature Reviews …, 2023 - nature.com
Cells have evolved a complex network of biochemical pathways, collectively known as the
DNA damage response (DDR), to prevent detrimental mutations from being passed on to …

PARP inhibitor resistance: the underlying mechanisms and clinical implications

H Li, ZY Liu, N Wu, YC Chen, Q Cheng, J Wang - Molecular cancer, 2020 - Springer
Due to the DNA repair defect, BRCA1/2 deficient tumor cells are more sensitive to PARP
inhibitors (PARPi) through the mechanism of synthetic lethality. At present, several PAPRi …

Integrative clinical genomics of advanced prostate cancer

D Robinson, EM Van Allen, YM Wu, N Schultz… - Cell, 2015 - cell.com
Toward development of a precision medicine framework for metastatic, castration-resistant
prostate cancer (mCRPC), we established a multi-institutional clinical sequencing …

DNA repair dysregulation from cancer driver to therapeutic target

NJ Curtin - Nature Reviews Cancer, 2012 - nature.com
Dysregulation of DNA damage repair and signalling to cell cycle checkpoints, known as the
DNA damage response (DDR), is associated with a predisposition to cancer and affects …

[HTML][HTML] ATM and ATR as therapeutic targets in cancer

AM Weber, AJ Ryan - Pharmacology & therapeutics, 2015 - Elsevier
In order to maintain genomic stability, cells have developed sophisticated signalling
pathways to enable DNA damage or DNA replication stress to be resolved. Key mediators of …

AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity

JHL Fok, A Ramos-Montoya… - Nature …, 2019 - nature.com
DNA-dependent protein kinase (DNA-PK) is a critical player in the DNA damage response
(DDR) and instrumental in the non-homologous end-joining pathway (NHEJ) used to detect …

ATM mutations in cancer: therapeutic implications

M Choi, T Kipps, R Kurzrock - Molecular cancer therapeutics, 2016 - AACR
Activation of checkpoint arrest and homologous DNA repair are necessary for maintenance
of genomic integrity during DNA replication. Germ-line mutations of the ataxia telangiectasia …

[HTML][HTML] RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer

C Cruz, M Castroviejo-Bermejo, S Gutiérrez-Enríquez… - Annals of …, 2018 - Elsevier
ABSTRACT Background BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired
homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents …

The poly (ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial

SK Sandhu, WR Schelman, G Wilding, V Moreno… - The lancet …, 2013 - thelancet.com
Background Poly (ADP-ribose) polymerase (PARP) is implicated in DNA repair and
transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP …

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next‐generation sequencing with a 25‐gene panel

N Tung, C Battelli, B Allen, R Kaldate, S Bhatnagar… - Cancer, 2015 - Wiley Online Library
BACKGROUND Next‐generation sequencing (NGS) allows for simultaneous sequencing of
multiple cancer susceptibility genes and, for an individual, may be more efficient and less …