ArticleMolecular cancer therapeutics2013
Targeting aberrant DNA double-strand break repair in triple-negative breast cancer with alpha-particle emitter radiolabeled anti-EGFR antibody.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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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.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
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- An integrative multi-omics landscape of multi-dimensional cellular stress and metabolic reprogramming in melanoma treated with targeted alpha therapy.Journal of nanobiotechnology · 2026Article
- Article
- Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.Molecular imaging and biology · 2023Review
- Transport-driven engineering of liposomes for delivery of α-particle radiotherapy to solid tumors: effect on inhibition of tumor progression and onset delay of spontaneous metastases.European journal of nuclear medicine and molecular imaging · 2021Article
- Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside.Pharmaceutics · 2021Review
- Current Status of Radiopharmaceutical Therapy.International journal of radiation oncology, biology, physics · 2021Review
- Modeling bystander effects that cause growth delay of breast cancer xenografts in bone marrow of mice treated with radium-223.International journal of radiation biology · 2021Article
- Combination Strategies to Improve Targeted Radionuclide Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Dosimetry, Radiobiology and Synthetic Lethality: Radiopharmaceutical Therapy (RPT) With Alpha-Particle-Emitters.Seminars in nuclear medicine · 2020Review
- The Case for Dosimetry in Alpha-Emitter Therapy.Journal of medical imaging and radiation sciences · 2019Review
- Cellular and Genetic Determinants of the Sensitivity of Cancer to α-Particle Irradiation.Cancer research · 2019Article
- DNA damage in human whole blood caused by radiopharmaceuticals evaluated by the comet assay.Mutagenesis · 2019Article
- Article
- Targeted and Nontargeted α-Particle Therapies.Annual review of biomedical engineering · 2018Review
- Production of a germline-humanized cetuximab scFv and evaluation of its activity in recognizing EGFR- overexpressing cancer cells.Human vaccines & immunotherapeutics · 2018Article
- Article
- Combined drug therapeutic strategies for the effective treatment of Triple Negative Breast Cancer.Bioscience reports · 2018Review
- Targeted α-Particle Radiation Therapy of HER1-Positive Disseminated Intraperitoneal Disease: An Investigation of the Human Anti-EGFR Monoclonal Antibody, Panitumumab.Translational oncology · 2017Article
- An agent-based model of triple-negative breast cancer: the interplay between chemokine receptor CCR5 expression, cancer stem cells, and hypoxia.BMC systems biology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The higher potential efficacy of alpha-particle radiopharmaceutical therapy lies in the 3- to 8-fold greater relative biological effectiveness (RBE) of alpha particles relative to photon or beta-particle radiation. This greater RBE, however, also applies to normal tissue, thereby reducing the potential advantage of high RBE. As alpha particles typically cause DNA double-strand breaks (DSB), targeting tumors that are defective in DSB repair effectively increases the RBE, yielding a secondary, RBE-based differentiation between tumor and normal tissue that is complementary to conventional, receptor-mediated tumor targeting. In some triple-negative breast cancers (TNBC; ER(-)/PR(-)/HER-2(-)), germline mutation in BRCA-1, a key gene in homologous recombination DSB repair, predisposes patients to early onset of breast cancer. These patients have few treatment options once the cancer has metastasized. In this study, we investigated the efficacy of alpha-particle emitter, (213)Bi-labeled anti-EGF receptor antibody, cetuximab, in BRCA-1-defective TNBC. (213)Bi-cetuximab was found to be significantly more effective in the BRCA-1-mutated TNBC cell line HCC1937 than BRCA-1-competent TNBC cell MDA-MB-231. siRNA knockdown of BRCA-1 or DNA-dependent protein kinase, catalytic subunit (DNA-PKcs), a key gene in non-homologous end-joining DSB repair pathway, also sensitized TNBC cells to (213)Bi-cetuximab. Furthermore, the small-molecule inhibitor of DNA-PKcs, NU7441, sensitized BRCA-1-competent TNBC cells to alpha-particle radiation. Immunofluorescent staining of γ-H2AX foci and comet assay confirmed that enhanced RBE is caused by impaired DSB repair. These data offer a novel strategy for enhancing conventional receptor-mediated targeting with an additional, potentially synergistic radiobiological targeting that could be applied to TNBC.
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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.