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 …

Hallmarks of DNA replication stress

S Saxena, L Zou - Molecular cell, 2022 - cell.com
Faithful DNA replication is critical for the maintenance of genomic integrity. Although DNA
replication machinery is highly accurate, the process of DNA replication is constantly …

Cell cycle checkpoints and beyond: Exploiting the ATR/CHK1/WEE1 pathway for the treatment of PARP inhibitor–resistant cancer

N Gupta, TT Huang, S Horibata, JM Lee - Pharmacological research, 2022 - Elsevier
Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have become a
mainstay of therapy in ovarian cancer and other malignancies, including BRCA-mutant …

[HTML][HTML] ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms

W Leung, A Simoneau, S Saxena, J Jackson, PS Patel… - Cell reports, 2023 - cell.com
The ATR kinase safeguards genomic integrity during S phase, but how ATR protects DNA
replication forks remains incompletely understood. Here, we combine four distinct assays to …

Targeting the DNA damage response for cancer therapy by inhibiting the kinase Wee1

AB Bukhari, GK Chan, AM Gamper - Frontiers in Oncology, 2022 - frontiersin.org
Cancer cells typically heavily rely on the G2/M checkpoint to survive endogenous and
exogenous DNA damage, such as genotoxic stress due to genome instability or radiation …

Increased replication origin firing links replication stress to whole chromosomal instability in human cancer

N Böhly, AK Schmidt, X Zhang, BO Slusarenko… - Cell Reports, 2022 - cell.com
Chromosomal instability (CIN) is a hallmark of cancer and comprises structural CIN (S-CIN)
and numerical or whole chromosomal CIN (W-CIN). Recent work indicated that replication …

DPPA5A suppresses the mutagenic TLS and MMEJ pathways by modulating the cryptic splicing of Rev1 and Polq in mouse embryonic stem cells

F Jiang, L Wang, Y Dong, W Nie… - Proceedings of the …, 2023 - National Acad Sciences
Genetic alterations are often acquired during prolonged propagation of pluripotent stem
cells (PSCs). This ruins the stem cell quality and hampers their full applications …

AKT1 interacts with DHX9 to Mitigate R Loop–Induced Replication Stress in Ovarian Cancer

TT Huang, CY Chiang, JR Nair, KM Wilson, K Cheng… - Cancer Research, 2024 - AACR
PARP inhibitor (PARPi)–resistant BRCA-mutant (BRCAm) high-grade serous ovarian cancer
(HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we …

Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation

O Brison, S Gnan, D Azar, S Koundrioukoff… - Nature Structural & …, 2023 - nature.com
Genome integrity requires replication to be completed before chromosome segregation. The
DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting CDK1, which …

Targeting the DNA damage response machinery for lung cancer treatment

KN Venugopala - Pharmaceuticals, 2022 - mdpi.com
Lung cancer is considered the most commonly diagnosed cancer and one of the leading
causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and …