ArticleJournal of experimental & clinical cancer research : CR2026
Impairment of oxidative metabolism compromises Rad51 recruitment and potentiates PARP inhibitor effectiveness in ovarian cancer.
Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundThe treatment of ovarian cancer has significantly improved since the introduction of PARP inhibitors (PARPi), small molecules designed to directly target and kill cancer cells with deficiencies in homologous recombination (HR) pathway. However, nearly half of patients present with HR-proficient tumors, rendering them not eligible for PARPi-based therapies and underscoring the urgent need for alternative treatment strategies.
methodsOxidative metabolism has been altered either by silencing the mitochondria regulator PGC-1β or by using the OXPHOS inhibitor IACS-010759. The metabolic alterations were characterized by seahorse analysis and metabolomic profiling. DNA damage and repair were evaluated by immunofluorescence and confocal analysis. Efficacy and tolerability of the combination of PARP and OXPHOS inhibitors were investigated in preclinical trials employing patient-derived ovarian cancer xenografts.
resultsOur findings reveal that PGC-1β silencing sensitizes ovarian cancer cells to PARPi by impairing oxidative metabolism, reducing succinate levels and decreasing Fen1 succinylation and SUMOylation. The impairment of these post-translational modifications hinders Fen1 activation and prevents the recruitment of Rad51, resulting in a HR-deficient-like phenotype. The translational relevance of the findings has been validated using the OXPHOS inhibitor IACS-010759, which synergizes with PARPi to inhibit cancer cell proliferation, while sparing normal cells. Furthermore, the combination therapy delays tumor progression in ovarian cancer xenografts not responsive to PARPi, independently from their HR status.
conclusionsTargeting mitochondrial metabolism depicts a novel mechanism to modulate DNA repair and enhance PARPi sensitivity. This approach broadens the therapeutic applicability of PARP inhibitors beyond HR-deficient tumors and offers promising avenues to overcome resistance in ovarian cancer treatment.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.