ArticleJournal of cancer research and clinical oncology2019
PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines.
Article in Journal of cancer research and clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1-Mutant Breast Cancer.Cancer research · 2026Article
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Complete remission with olaparib in BRIP1-mutated metastatic high-grade pleomorphic sarcoma: case study and literature review - an example of a genomic profiling-based tumor treatment, in a cancer type with high unmet clinical need.Acta oncologica (Stockholm, Sweden) · 2025Review
- Emerging innovations in theranostics for pancreatic neuroendocrine tumors.NPJ precision oncology · 2025Review
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- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
- Children's Oncology Group's 2023 blueprint for research: Soft tissue sarcomas.Pediatric blood & cancer · 2023Article
- Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma.International journal of molecular sciences · 2022Review
- 1,3-diarylpyrazolones as potential anticancer agents for non-small cell lung cancer: Synthesis and antiproliferative activity evaluation.Chemical biology & drug design · 2022Article
- PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer.Pathology oncology research : POR · 2022Article
- Radioresistance in rhabdomyosarcomas: Much more than a question of dose.Frontiers in oncology · 2022Review
- The botanical drug PBI-05204, a supercritical COFrontiers in pharmacology · 2022Article
- Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses.Cell discovery · 2021Review
- Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels: a new perspective for Parp1 inhibition.Cell death & disease · 2021Article
- MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells.International journal of molecular sciences · 2021Article
- Molecular mechanisms of chemo- and radiotherapy resistance and the potential implications for cancer treatment.MedComm · 2021Review
- Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Journal of clinical medicine · 2021Review
- Combination Strategies to Improve Targeted Radionuclide Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo.Journal of cancer research and clinical oncology · 2020Article
- Article
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR).
methodsCell viability was monitored by trypan blue exclusion dye assays. Cell cycle progression and apoptosis were measured by flow cytometry, and alterations of specific molecular markers were investigated by, Real Time PCR, Western blotting and immunofluorescence experiments. Irradiations were carried out at a dose rate of 2 Gy (190 UM/min) or 4 Gy (380 UM/min). Radiosensitivity was assessed by using clonogenic assays.
resultsOlaparib and AZD2461 dose-dependently reduced growth of both RH30 and RD cells by arresting growth at G2/M phase and by modulating the expression, activation and subcellular localization of specific cell cycle regulators. Downregulation of phospho-AKT levels and accumulation of γH2AX, a specific marker of DNA damage, were significantly and persistently induced by Olaparib and AZD2461 exposure, this leading to apoptosis-related cell death. Both PARPi significantly enhanced the effects of IR by accumulating DNA damage, increasing G2 arrest and drastically reducing the clonogenic capacity of RMS-cotreated cells.
conclusionsThis study suggests that the combined exposure to PARPi and IR might display a role in the treatment of RMS tumours compared with single-agent exposure, since stronger cytotoxic effects are induced, and compensatory survival mechanisms are prevented.
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