Nucleotide metabolism: a pan-cancer metabolic dependency

NJ Mullen, PK Singh - Nature Reviews Cancer, 2023‏ - nature.com
Metabolic alterations are a key hallmark of cancer cells, and the augmented synthesis and
use of nucleotide triphosphates is a critical and universal metabolic dependency of cancer …

Targeting replication stress in cancer therapy

AABA da Costa, D Chowdhury, GI Shapiro… - Nature reviews Drug …, 2023‏ - nature.com
Replication stress is a major cause of genomic instability and a crucial vulnerability of
cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that …

Chemotherapy induces senescence-like resilient cells capable of initiating AML recurrence

C Duy, M Li, M Teater, C Meydan, FE Garrett-Bakelman… - Cancer discovery, 2021‏ - AACR
Patients with acute myeloid leukemia (AML) frequently relapse after chemotherapy, yet the
mechanism by which AML reemerges is not fully understood. Herein, we show that primary …

Biomarker-guided development of DNA repair inhibitors

JM Cleary, AJ Aguirre, GI Shapiro, AD D'Andrea - Molecular cell, 2020‏ - cell.com
Anti-cancer drugs targeting the DNA damage response (DDR) exploit genetic or functional
defects in this pathway through synthetic lethal mechanisms. For example, defects in …

DNA damage checkpoint kinases in cancer

HL Smith, H Southgate, DA Tweddle… - Expert reviews in …, 2020‏ - cambridge.org
DNA damage response (DDR) pathway prevents high level endogenous and environmental
DNA damage being replicated and passed on to the next generation of cells via an …

Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial

PA Konstantinopoulos, SC Cheng… - The Lancet …, 2020‏ - thelancet.com
Background High-grade serous ovarian cancers show increased replication stress,
rendering cells vulnerable to ATR inhibition because of near universal loss of the G1/S …

Ribonucleotide reductases: structure, chemistry, and metabolism suggest new therapeutic targets

BL Greene, G Kang, C Cui, M Bennati… - Annual review of …, 2020‏ - annualreviews.org
Ribonucleotide reductases (RNRs) catalyze the de novo conversion of nucleotides to
deoxynucleotides in all organisms, controlling their relative ratios and abundance. In doing …

Targeting ATR as Cancer Therapy: A new era for synthetic lethality and synergistic combinations?

A Bradbury, S Hall, N Curtin, Y Drew - Pharmacology & therapeutics, 2020‏ - Elsevier
The DNA damage response (DDR) machinery is responsible for detecting DNA damage,
pausing the cell cycle and initiating DNA repair. Ataxia telangiectasia and Rad3-related …

A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer

PA Konstantinopoulos, AABA da Costa… - Nature …, 2021‏ - nature.com
In a trial of patients with high grade serous ovarian cancer (HGSOC), addition of the ATR
inhibitor berzosertib to gemcitabine improved progression free survival (PFS) compared to …

Targeting the replication stress response through synthetic lethal strategies in cancer medicine

NYL Ngoi, MM Pham, DSP Tan, TA Yap - Trends in cancer, 2021‏ - cell.com
The replication stress response (RSR) involves a downstream kinase cascade comprising
ataxia telangiectasia-mutated (ATM), ATM and rad3-related (ATR), checkpoint kinases 1 and …