ArticlePloS one2017
Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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.
A Phase I Study of SGI-110 Combined With Irinotecan Followed by a Randomized Phase II Study of SGI-110 Combined With Irinotecan Versus Regorafenib or TAS-102 in Previously Treated Metastatic Colorectal Cancer Patients
Optimizing and Personalising Azacitidine Combination Therapy for Treating Solid Tumours Using the Quadratic Phenotypic Optimization Platform (QPOP) and an Artificial Intelligence-based Platform (CURATE.AI)
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The mechanisms and drug therapies of colorectal cancer and epigenetics: bibliometrics and visualized analysis.Frontiers in pharmacology · 2024Pooled it
- Getting the right combination to break the epigenetic code.Nature reviews. Clinical oncology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction.International journal of molecular sciences · 2024Review
- Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling.Science advances · 2024Article
- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.International journal of molecular sciences · 2023Review
- Restoration of MiR-34a Expression by 5-Azacytidine Augments Alimta -Induced Cell Death in Non-Small Lung Cancer Cells by Downregulation of HMG B1, A2 and Bcl-2 Pathway.Cell journal · 2021Article
- Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.Environmental science and pollution research international · 2021Review
- Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer.Frontiers in oncology · 2021Article
- Advances in CpG Island Methylator Phenotype Colorectal Cancer Therapies.Frontiers in oncology · 2021Review
- Age-Related Macular Degeneration: From Epigenetics to Therapeutic Implications.Advances in experimental medicine and biology · 2021Article
- Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance.Frontiers in pharmacology · 2021Review
- Review
- Review
- Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- Correction: Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells.PloS one · 2020Article
- Modulation of the Endothelin System in Colorectal Cancer Liver Metastasis: Influence of Epigenetic Mechanisms?Frontiers in pharmacology · 2020Article
- Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies.World journal of stem cells · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment. For irinotecan (IRI), growth diminished by 16-62 fold as assessed, by both proliferation (IC50) and anchorage independent cell growth soft agar assays. Treatment of resistant HCT116 cell line along with in-vivo, for CRC line xenografts, AZA plus IRI again exhibits this synergistic response with significant improvement in survival and tumor regression in the mice. Genome-wide expression correlates changes in pathways for cell adhesion and DNA repair with the above responses. A Phase 1/2 clinical trial testing this concept is already underway testing the clinical efficacy of this concept in IRI resistant, metastatic CRC (NCT01896856).
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.