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 …

Understanding and overcoming resistance to PARP inhibitors in cancer therapy

MP Dias, SC Moser, S Ganesan… - Nature reviews Clinical …, 2021 - nature.com
Developing novel targeted anticancer therapies is a major goal of current research. The use
of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with homologous …

TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes

NM Tung, ME Robson, S Ventz… - Journal of Clinical …, 2020 - ascopubs.org
PURPOSE Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved
for the treatment of human epidermal growth factor receptor 2 (HER2)–negative metastatic …

Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase …

J Mateo, N Porta, D Bianchini, U McGovern… - The Lancet …, 2020 - thelancet.com
Background Metastatic castration-resistant prostate cancer is enriched in DNA damage
response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the …

PARP and PARG inhibitors in cancer treatment

D Slade - Genes & development, 2020 - genesdev.cshlp.org
Oxidative and replication stress underlie genomic instability of cancer cells. Amplifying
genomic instability through radiotherapy and chemotherapy has been a powerful but …

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 …

[HTML][HTML] A decade of clinical development of PARP inhibitors in perspective

J Mateo, CJ Lord, V Serra, A Tutt, J Balmaña… - Annals of …, 2019 - Elsevier
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; …

[HTML][HTML] ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer

RE Miller, A Leary, CL Scott, V Serra, CJ Lord… - Annals of …, 2020 - Elsevier
Background Homologous recombination repair deficiency (HRD) is a frequent feature of
high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is …

Leveraging the replication stress response to optimize cancer therapy

E Cybulla, A Vindigni - Nature Reviews Cancer, 2023 - nature.com
High-fidelity DNA replication is critical for the faithful transmission of genetic information to
daughter cells. Following genotoxic stress, specialized DNA damage tolerance pathways …

PARP inhibitor resistance: a tug-of-war in BRCA-mutated cells

SM Noordermeer, H van Attikum - Trends in cell biology, 2019 - cell.com
Poly-(ADP)-ribose polymerase (PARP) inhibition is synthetic lethal with deficiency for
homologous recombination (HR), a pathway essential for DNA double-strand break repair …