ArticleClinical and translational medicine2021
LRRK2 inhibition potentiates PARP inhibitor cytotoxicity through inhibiting homologous recombination-mediated DNA double strand break repair.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Pooled it
- Whole-Exome Sequencing Identifies Candidate Genomic Features Associated with Response to Platinum-Based Chemotherapy and Ixabepilone-Based Treatment in Ovarian Cancer.International journal of molecular sciences · 2026Article
- Novel Exploratory Transcriptomic Candidates as Biomarkers and Cancer Hallmark Fingerprints for Ovarian Endometroid and Clear Cell Carcinomas in Women.Antioxidants (Basel, Switzerland) · 2026Article
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- SLX1 silencing overcomes Olaparib resistance in metastatic castration-resistant prostate cancer by disrupting SLX4-mediated DNA repair complexes.Cancer biology & therapy · 2025Article
- SLX1 Inhibition Enhances Olaparib Sensitivity by Impairing Homologous Recombination Repair in Breast Cancer.International journal of molecular sciences · 2025Article
- Aberrant accumulation of phosphorylated BRCA1 in brainstem-type and cortical-type Lewy bodies in Lewy body disease.Journal of neuropathology and experimental neurology · 2025Article
- Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma.Open life sciences · 2024Article
- Deregulated kinase action in prostate cancer: molecular basis and therapeutic implications.Endocrine-related cancer · 2023Review
- DNA Damage-Mediated Neurotoxicity in Parkinson's Disease.International journal of molecular sciences · 2023Review
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- Decoding the Role of Familial Parkinson's Disease-Related Genes in DNA Damage and Repair.Aging and disease · 2022Article
- Review
- LRRK2 inhibition potentiates PARP inhibitor cytotoxicity through inhibiting homologous recombination-mediated DNA double strand break repair.Clinical and translational medicine · 2021Article
- An Analysis Regarding the Prognostic Significance of MAVS and Its Underlying Biological Mechanism in Ovarian Cancer.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 3 countries.
Funding
Abstract
PARP inhibitors induce DNA lesions, the repair of which are highly dependent on homologous recombination (HR), and preferentially kill HR- deficient cancers. However, cancer cells have developed several mechanisms to transform HR and confer drug resistance to PARP inhibition. Therefore, there is a great clinical interest in exploring new therapies that induce HR deficiency (HRD), thereby sensitizing cancer cells to PARP inhibitors. Here, we found that GSK2578215A, a high-selective and effective leucine-rich repeat kinase 2 (LRRK2) inhibitor, or LRRK2 depletion suppresses HR preventing the recruitment of RAD51 to DNA damage sites through disruption of the interaction of RAD51 and BRCA2. Moreover, LRRK2 inhibition or depletion increases the susceptibility of ovarian cancer cells to Olaparib in vitro and in vivo. In clinical specimens, LRRK2 high expression is high related with advanced clinical characteristics and poor survival of ovarian cancer patients. All these findings indicate ovarian cancers expressing high levels of LRRK2 are more resistant to treatment potentially through promoting HR. Furthermore, combination treatment with an LRRK2 and PARP inhibitor may be a novel strategy to improve the effectiveness of LRRK2 expression ovarian 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.