The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo.

@article{Weston2010ThePI,
  title={The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo.},
  author={Victoria J. Weston and Ceri E Oldreive and Anna Skowrońska and David Oscier and Guy Pratt and Martin J. S. Dyer and Graeme C.M. Smith and Judith E. Powell and Zbigniew Rudzki and Pamela R. Kearns and Paul Moss and A. Malcolm R. Taylor and Tatjana Stankovic},
  journal={Blood},
  year={2010},
  volume={116 22},
  pages={
          4578-87
        }
}
The Ataxia Telangiectasia Mutated (ATM) gene is frequently inactivated in lymphoid malignancies such as chronic lymphocytic leukemia (CLL), T-prolymphocytic leukemia (T-PLL), and mantle cell lymphoma (MCL) and is associated with defective apoptosis in response to alkylating agents and purine analogues. ATM mutant cells exhibit impaired DNA double strand break repair. Poly (ADP-ribose) polymerase (PARP) inhibition that imposes the requirement for DNA double strand break repair should selectively… 
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Olaparib Induced Moderate Killing of ATM -Deficient Mantle Cell Lymphoma Cells In Vitro and In Vivo

In vitro and in vivo sensitivity to the PARP inhibitor olaparib in the ATM deficient mantle cell lymphoma cell line Granta-519 is investigated and decreased proliferation in vitro and vivo is confirmed.

ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib1

Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53

It is shown that mantle cell lymphoma (MCL) cells deficient in both ATM and p53 are more sensitive to the PARP inhibitor olaparib than cells lacking ATM function alone, and the combination of ATM and PARP inhibitors may have utility in targeting p53‐deficient malignancies.

Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells

It is shown that olaparib combines synergistically with the ATR-inhibitor AZD6738, in vitro, leading to selective cell death in ATM-deficient cells, suggesting that combined treatment could circumvent the need for prolonged drug exposure.

Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines

It is reported that PARP inhibitors can potentially target ATM deficiency arising in a solid malignancy and combined inhibition of ATM and PARP-1 is a rational strategy for expanding the utility of PARp-1 inhibitors to gastric cancer with p53 disruption.

ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells.

In TP53- or ATM-defective CLL cells, inhibition of ATR signaling by AZD6738 led to an accumulation of unrepaired DNA damage, which was carried through into mitosis because of defective cell cycle checkpoints, resulting in cell death by mitotic catastrophe.

ATM-depletion in breast cancer cells confers sensitivity to PARP inhibition

It is indicated that ATM-depletion can sensitize breast cancer cells to PARP inhibition, suggesting a potential in the treatment of breast cancers low in ATM protein expression/activity, such as those arising in mutant ATM heterozygous carriers.

Poly (ADP-ribose) polymerase inhibitors selectively induce cytotoxicity in TCF3-HLF-positive leukemic cells.

Targeting ATM-deficient CLL through interference with DNA repair pathways

The role of ATM signaling for the immediate DNA damage response, DNA repair and leukemogenesis is focused on and the potential use of PARP1 and DNA-PKcs inhibitors for the treatment of ATM-mutant CLL clones are highlighted.

PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia

PARP activity is highly variable in CLL and correlates with stress-induced proteins, and Proliferating CLL cells (including those with p53 or ATM loss) are highly sensitive to the PARP inhibitor talazoparib.
...

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