ArticleOncotarget2019
Synthetic lethality of a cell-penetrating anti-RAD51 antibody in PTEN-deficient melanoma and glioma cells.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Advancements in cell-penetrating monoclonal antibody treatment.Oncotarget · 2024Article
- Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition.Oncotarget · 2024Article
- Advances in synthetic lethality modalities for glioblastoma multiforme.Open medicine (Warsaw, Poland) · 2024Review
- Article
- Roles of homologous recombination in response to ionizing radiation-induced DNA damage.International journal of radiation biology · 2023Review
- Article
- Targeting RAD51-Mediated Homologous Recombination as a Treatment for Advanced Solid and Hematologic Malignancies: Opportunities and Challenges Ahead.OncoTargets and therapy · 2022Review
- ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody.JCI insight · 2021Article
- A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death.Cell chemical biology · 2021Article
- Targeting Genome Stability in Melanoma-A New Approach to an Old Field.International journal of molecular sciences · 2021Review
- Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Review
- Article
- Targeting Rad51 as a strategy for the treatment of melanoma cells resistant to MAPK pathway inhibition.Cell death & disease · 2020Article
- Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases.Trends in molecular medicine · 2019Review
- The Mechanisms Underlying PTEN Loss in Human Tumors Suggest Potential Therapeutic Opportunities.Biomolecules · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
PTEN is a tumor suppressor that is highly mutated in a variety of human cancers. Recent studies have suggested a link between PTEN loss and deficiency in the non-homologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair. As a means to achieve synthetic lethality in this context, we tested the effect of 3E10, a cell-penetrating autoantibody that inhibits RAD51, a key factor in the alternative pathway of DSB repair, homology dependent repair (HDR). We report here that treatment of PTEN-deficient glioma cells with 3E10 leads to an accumulation of DNA damage causing decreased proliferation and increased cell death compared to isogenic PTEN proficient controls. Similarly, 3E10 was synthetically lethal to a series of PTEN-deficient, patient-derived primary melanoma cell populations. Further, 3E10 was found to synergize with a small molecule inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein, a DNA damage checkpoint kinase, in both PTEN-deficient glioma cells and primary melanoma cells. These results point to a targeted synthetic lethal strategy to treat PTEN-deficient cancers through a combination designed to disrupt both DNA repair and DNA damage checkpoint signaling.
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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.