ArticleOncotarget2017
The novel ATM inhibitor (AZ31) enhances antitumor activity in patient derived xenografts that are resistant to irinotecan monotherapy.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- The Development of ATM Inhibitors in Cancer Therapy.Targeted oncology · 2025Review
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing.Nature communications · 2023Article
- Patient-derived xenograft model in colorectal cancer basic and translational research.Animal models and experimental medicine · 2023Review
- ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer.BMC cancer · 2022Article
- Assessing the performance of different outcomes for tumor growth studies with animal models.Animal models and experimental medicine · 2022Article
- Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer.Cancers · 2022Review
- Sensors and Inhibitors for the Detection of Ataxia Telangiectasia Mutated (ATM) Protein Kinase.Molecular pharmaceutics · 2021Review
- Review
- Case Report: Combination of Olaparib With Chemotherapy in a Patient With ATM-Deficient Colorectal Cancer.Frontiers in oncology · 2021Article
- HSATII RNA is induced via a noncanonical ATM-regulated DNA damage response pathway and promotes tumor cell proliferation and movement.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib.Therapeutic advances in medical oncology · 2020Article
- ATM Dysfunction in Pancreatic Adenocarcinoma and Associated Therapeutic Implications.Molecular cancer therapeutics · 2019Review
- ATM Is Required for the Repair of Oxaliplatin-Induced DNA Damage in Colorectal Cancer.Clinical colorectal cancer · 2018Article
- pRAD50: a novel and clinically applicable pharmacodynamic biomarker of both ATM and ATR inhibition identified using mass spectrometry and immunohistochemistry.British journal of cancer · 2018Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by generating double strand breaks resulting in DNA damage. The activation of the ATM pathway plays a fundamental role in regulating the cellular response and repair to DNA damage. The objective of this preclinical study was to determine whether ATM inhibition would enhance sensitivity to irinotecan treatment. Treatment effects of AZ31, irinotecan or AZ31 + irinotecan were investigated in CRC cell lines and CRC patient derived xenografts. Activation of ATM and downstream targets p-RAD50 and p-H2AX were evaluated by immunohistochemistry. Combinational effects were demonstrated in 4 out of 8 CRC explants. Interestingly, each of the combinational sensitive CRC PDX models were shown to be more resistant to irinotecan single agent therapy. Treatment with irinotecan significantly elevated the ATM pathway evident by an increase in the activation of H2AX and RAD50. Combinational therapy reduced the activation of H2AX and RAD50 when compared to irinotecan alone in the combination sensitive CRC098. AZ31 + irinotecan was effective at reducing tumor growth in tumors that exhibited resistance to irinotecan in our CRC PDX model. These findings support further investigation of this combinational therapy for the treatment of CRC patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.