ArticleGynecologic oncology2015
Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells.
Article in Gynecologic oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 108 citations in OpenAlex.
- Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017.Cancer letters · 2021Trial
- A targetable OSGIN1 - AMPK - SLC2A3 axis controls the vulnerability of ovarian cancer to ferroptosis.NPJ precision oncology · 2025Article
- ATRX loss inhibits DDR to strengthen radio-sensitization in p53-deficent HCT116 cells.Scientific reports · 2025Article
- High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- The KRAS, ATR and CHEK1 expression levels in endometrial cancer are the risk factors predicting recurrence.PloS one · 2024Article
- Targeting DNA Damage Repair and Immune Checkpoint Proteins for Optimizing the Treatment of Endometrial Cancer.Pharmaceutics · 2023Review
- Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?Journal of clinical medicine · 2023Review
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Association of variations in theFrontiers in pharmacology · 2023Article
- Fighting resistance: post-PARP inhibitor treatment strategies in ovarian cancer.Therapeutic advances in medical oncology · 2023Review
- Improving cervical cancer survival-A multifaceted strategy to sustain progress for this global problem.Cancer · 2022Review
- ATR Inhibitors in Platinum-Resistant Ovarian Cancer.Cancers · 2022Review
- Observation of the cervical microbiome in the progression of cervical intraepithelial neoplasia.BMC cancer · 2022Article
- Pharmacologic inhibition of ataxia telangiectasia and Rad3-related (ATR) in the treatment of head and neck squamous cell carcinoma.Molecular carcinogenesis · 2022Review
- Molecular mechanisms of long noncoding RNAs associated with cervical cancer radiosensitivity.Frontiers in genetics · 2022Review
- ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage.American journal of cancer research · 2022Article
- Radiation induces NORAD expression to promote ESCC radiotherapy resistance via EEPD1/ATR/Chk1 signalling and by inhibiting pri-miR-199a1 processing and the exosomal transfer of miR-199a-5p.Journal of experimental & clinical cancer research : CR · 2021Article
- Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models.International journal of molecular sciences · 2021Article
- Sensors and Inhibitors for the Detection of Ataxia Telangiectasia Mutated (ATM) Protein Kinase.Molecular pharmaceutics · 2021Review
- Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveSignificant reductions in gynecologic (GYN) cancer mortality and morbidity require treatments that prevent and reverse resistance to chemotherapy and radiation. The objective of this study was to determine if pharmacologic inhibition of key DNA damage response kinases in GYN cancers would enhance cell killing by platinum-based chemotherapy and radiation.
methodsA panel of human ovarian, endometrial and cervical cancer cell lines were treated with platinum drugs or ionizing radiation (IR) along with small molecule pharmacological kinase inhibitors of Ataxia telangiectasia mutated (ATM) and ATM and Rad-3-related (ATR).
resultsPharmacologic inhibition of ATR significantly enhanced platinum drug response in all GYN cancer cell lines tested, whereas inhibition of ATM did not enhance the response to platinum drugs. Co-inhibition of ATM and ATR did not enhance platinum kill beyond that observed by inhibition of ATR alone. By contrast, inhibiting either ATR or ATM enhanced the response to IR in all GYN cancer cells, with further enhancement achieved with co-inhibition.
conclusionsThese studies highlight actionable mechanisms operative in GYN cancer cells with potential to maximize response of platinum agents and radiation in newly diagnosed as well as recurrent gynecologic cancers.
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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.