ArticleJournal of ovarian research2021
Molecular response to PARP1 inhibition in ovarian cancer cells as determined by mass spectrometry based proteomics.
Article in Journal of ovarian research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Trial
- Subtype-specific mechanisms of lipid metabolism in gynecological malignancies and novel targeted intervention strategies (Review).Oncology letters · 2026Review
- Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.Clinical epigenetics · 2025Article
- Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review).Molecular medicine reports · 2025Review
- Mass Spectrometry-Based Proteomics for Classification and Treatment Optimisation of Triple Negative Breast Cancer.Journal of personalized medicine · 2024Review
- Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion.NPJ breast cancer · 2024Article
- scPerturb: harmonized single-cell perturbation data.Nature methods · 2024Article
- PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway.Oncogene · 2024Article
- Metabolic reprogramming of clear cell renal cell carcinoma.Frontiers in endocrinology · 2023Review
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundPoly (ADP)-ribose polymerase (PARP) inhibitors have entered routine clinical practice for the treatment of high-grade serous ovarian cancer (HGSOC), yet the molecular mechanisms underlying treatment response to PARP1 inhibition (PARP1i) are not fully understood.
methodsHere, we used unbiased mass spectrometry based proteomics with data-driven protein network analysis to systematically characterize how HGSOC cells respond to PARP1i treatment.
resultsWe found that PARP1i leads to pronounced proteomic changes in a diverse set of cellular processes in HGSOC cancer cells, consistent with transcript changes in an independent perturbation dataset. We interpret decreases in the levels of the pro-proliferative transcription factors SP1 and β-catenin and in growth factor signaling as reflecting the anti-proliferative effect of PARP1i; and the strong activation of pro-survival processes NF-κB signaling and lipid metabolism as PARPi-induced adaptive resistance mechanisms. Based on these observations, we nominate several protein targets for therapeutic inhibition in combination with PARP1i. When tested experimentally, the combination of PARPi with an inhibitor of fatty acid synthase (TVB-2640) has a 3-fold synergistic effect and is therefore of particular pre-clinical interest.
conclusionOur study improves the current understanding of PARP1 function, highlights the potential that the anti-tumor efficacy of PARP1i may not only rely on DNA damage repair mechanisms and informs on the rational design of PARP1i combination therapies in ovarian cancer.
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