Synthetic Lethality In CLL With DNA Damage Response Defect By Targeting ATR Pathway
Stankovic T,Nicholas D, Kwok M et al
Key Points:
Ataxia Telangiectasia Mutated (ATM) protein coordinates responses to DNA double strand breaks.
ATM-null status caused by biallelic ATM gene inactivation results in resistance to p53-dependent apoptosis.
Initiation of cell cycling required for both ATR upregulation and activation of ATR target Chk1 in response to replicating stress inducing agent hydroxyurea.
Uniform loss of cellular viability observed in presence of 1 or 3 μM of inhibitor in ATM-null cells but not in ATM-wt counterpart.
Observed reduction in tumour cell numbers in AZD6738-treated compared to vehicle-treated spleens.
Implications:
- Targeting ATR pathway provides an attractive approach.
Additional Comments:
- Preclinical study with interesting new pathway.
View the original abstract on the ASH website.
