ArticleCancer cell international2015
Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status.
Article in Cancer cell international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Poly-ADP-ribosylation modulated by poly(ADP-ribose) polymerase 1 is associated with glucose metabolism in colorectal cancer cells.Translational oncology · 2026Article
- Tumor cell-intrinsic PD-1 regulates chemotherapy resistance in colorectal cancer cells by activating downstream MAPK signaling.BJC reports · 2025Article
- Combination Therapy Using Phytochemicals and PARP Inhibitors in Hybrid Nanocarriers: An Optimistic Approach for the Management of Colon Cancer.International journal of molecular sciences · 2025Review
- PARP Inhibition in Colorectal Cancer-A Comparison of Potential Predictive Biomarkers for Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Targeted Treatment against Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024Review
- PARP Inhibitors in Colorectal Malignancies: A 2023 Update.Reviews on recent clinical trials · 2024Review
- A carrier-free supramolecular nano-twin-drug for overcoming irinotecan-resistance and enhancing efficacy against colorectal cancer.Journal of nanobiotechnology · 2023Article
- Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy.Clinical science (London, England : 1979) · 2022Article
- Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer.Cancers · 2022Review
- Fanconi Anemia Pathway in Colorectal Cancer: A Novel Opportunity for Diagnosis, Prognosis and Therapy.Journal of personalized medicine · 2022Review
- Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer.Nature cancer · 2022Article
- Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers.Biomedicines · 2021Review
- BRCA mutations and gastrointestinal cancers: When to expect the unexpected?World journal of clinical oncology · 2021Review
- Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment.World journal of gastrointestinal oncology · 2021Review
- Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.BMC cancer · 2021Article
- Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer.Frontiers in pharmacology · 2021Review
- Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures.Endocrinology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCells with homologous recombination (HR) deficiency, most notably caused by mutations in the BRCA1 or BRCA2 genes, are sensitive to PARP inhibition. Microsatellite instability (MSI) accounts for 10-15% of colorectal cancer (CRC) and is hypothesized to lead to HR defects due to altered expression of Mre11, a protein required for double strand break (DSB) repair. Indeed, others have reported that PARP inhibition is efficacious in MSI CRC.
methodsHere we examine the response to niraparib, a potent PARP-1/PARP-2 inhibitor currently under clinical evaluation, in MSI versus microsatellite stable (MSS) CRC cell lines in vitro and in vivo. We compiled a large panel of MSI and MSS CRC cell lines and evaluated the anti-proliferative activity of niraparib. In addition to testing single agent cytotoxic activity of niraparib, we also tested irinotecan (or SN-38, the active metabolite of irinotecan) activity alone and in combination with niraparib in vitro and in vivo.
resultsIn contrast to earlier reports, MSI CRC cell lines were not more sensitive to niraparib than MSS CRC cell lines¸ suggesting that the MSI phenotype does not sensitize CRC cell lines to PARP inhibition. Moreover, even the most sensitive MSI cell lines had niraparib EC50s greater than 10 fold higher than BRCA-deficient cell lines. However, MSI lines were more sensitive to SN-38 than MSS lines, consistent with previous findings. We have also demonstrated that combination of niraparib and irinotecan was more efficacious than either agent alone in both MSI and MSS cell lines both in vitro and in vivo, and that niraparib potentiates the effect of irinotecan regardless of MSI status.
conclusionsOur results support the clinical evaluation of this combination in all CRC patients, regardless of MSI status.
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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.