Nucleotide metabolism: a pan-cancer metabolic dependency
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 …
use of nucleotide triphosphates is a critical and universal metabolic dependency of cancer …
Targeting replication stress in cancer therapy
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 …
cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that …
Chemotherapy induces senescence-like resilient cells capable of initiating AML recurrence
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 …
mechanism by which AML reemerges is not fully understood. Herein, we show that primary …
Biomarker-guided development of DNA repair inhibitors
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 …
defects in this pathway through synthetic lethal mechanisms. For example, defects in …
DNA damage checkpoint kinases in cancer
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 …
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
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 …
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
Ribonucleotide reductases (RNRs) catalyze the de novo conversion of nucleotides to
deoxynucleotides in all organisms, controlling their relative ratios and abundance. In doing …
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?
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 …
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
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 …
inhibitor berzosertib to gemcitabine improved progression free survival (PFS) compared to …
Targeting the replication stress response through synthetic lethal strategies in cancer medicine
The replication stress response (RSR) involves a downstream kinase cascade comprising
ataxia telangiectasia-mutated (ATM), ATM and rad3-related (ATR), checkpoint kinases 1 and …
ataxia telangiectasia-mutated (ATM), ATM and rad3-related (ATR), checkpoint kinases 1 and …