ArticleInvestigational new drugs2019
Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.
Article in Investigational new drugs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- 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
- Alternative lengthening of telomere-based immortalization renders H3G34R-mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.Neuro-oncology · 2025Article
- Bioanalytical assay for the quantification of rucaparib in rat plasma using UPLC-MS/MS: development, and validation for interaction with myricetin.Frontiers in pharmacology · 2025Article
- Targeting PARP-1 and DNA Damage Response Defects in Colorectal Cancer Chemotherapy with Established and Novel PARP Inhibitors.Cancers · 2024Article
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- PARP Inhibitors in Colorectal Malignancies: A 2023 Update.Reviews on recent clinical trials · 2024Review
- Identification of disulfidptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in colorectal cancer.Journal of cancer research and clinical oncology · 2023Article
- A carrier-free supramolecular nano-twin-drug for overcoming irinotecan-resistance and enhancing efficacy against colorectal cancer.Journal of nanobiotechnology · 2023Article
- Alkylation of nucleobases by 2-chloro-NAR cancer · 2023Article
- Altered cytoplasmic and nuclear ADP-ribosylation levels analyzed with an improved ADP-ribose binder are a prognostic factor in renal cell carcinoma.The journal of pathology. Clinical research · 2023Article
- Polyadenosine diphosphate-ribose polymerase inhibitors: advances, implications, and challenges in tumor radiotherapy sensitization.Frontiers in oncology · 2023Review
- Anti-Colorectal Cancer Effects of a Novel Camptothecin Derivative PCC0208037Pharmaceuticals (Basel, Switzerland) · 2022Article
- Novel Set of Diarylmethanes to Target Colorectal Cancer: Synthesis,Biomolecules · 2022Article
- Article
- Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer.Cancers · 2022Review
- Peroxidase from foxtail millet bran exerts anti-colorectal cancer activityActa pharmaceutica Sinica. B · 2022Article
- Potentiating effect of reovirus on immune checkpoint inhibition in microsatellite stable colorectal cancer.Frontiers in oncology · 2022Article
- A Prognostic Gene Signature for Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers.Biomedicines · 2021Review
- Cytoplasmic ADP-ribosylation levels correlate with markers of patient outcome in distinct human cancers.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Intended to explore synthetic lethality and develop better combinatorial regimens, we screened colorectal cancer (CRC) cells using poly ADP-ribose (PAR) polymerase (PARP) inhibitors and cytotoxic agents. We studied four PARP inhibitors and three DNA-damaging agents, and their combinations using sulforhodamine B assay. Rucaparib demonstrated the greatest synergy with irinotecan, followed by olaparib and PJ34. Rucaparib and irinotecan was further subjected to detailed examination to determine combination index (CI) and underlying mechanism of action. Effectiveness and sequence dependence of this combination were assessed in microsatellite stable (MSS) and unstable (MSI) CRC and HCT116 isogenic cell lines. The degree of cell cycle arrest and apoptosis was determined by FACS. In vivo studies were performed to confirm efficacy of this combination. PAR levels in MSI and PARP expression in MSI and MSS cell lines were diminished upon combinatorial treatment. HCT116 isogenic cells revealed the importance of p21, p53 and PTEN in exerting synergy. In MSI cells, administration of rucaparib prior to irinotecan enhanced cytotoxicity compared to other strategies explored. FACS revealed S-phase arrest and increased late-stage apoptosis in MSS, and G2-M arrest and total and early-stage apoptosis in MSI cells. In in vivo murine xenograft models, a significant reduction in tumor volume and expression of Ki67, pancytokeratin and RPS6KB1, and increase in expression of caspase 3 were observed with the combination. In conclusion, among the various combinations studied, rucaparib plus irinotecan was the most synergistic one. Alterations in cell cycle arrest and apoptosis were dependent on MSI status in CRC cells.
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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.