ArticleMolecular cancer research : MCR2015
Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil.
Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting MCM6 Enhances Melphalan Chemosensitivity in Retinoblastoma by Modulating DNA Damage Response.Investigative ophthalmology & visual science · 2025Article
- TRIM21 promotes colorectal cancer development through regulating DNA replication by TCF3/MCM2/5 axis.Cell death discovery · 2025Article
- The Role of MCM7 and Its Hosted miR-106b-25 Cluster in Renal Cancer Progression.International journal of molecular sciences · 2025Article
- Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.Cancer research communications · 2025Article
- Identification of ATP-Competitive Human CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function.Molecular cancer therapeutics · 2024Article
- Mechanisms of Berberine in anti-pancreatic ductal adenocarcinoma revealed by integrated multi-omics profiling.Scientific reports · 2024Article
- Review
- Review
- Targeting the Unwindosome by Mebendazole Is a Vulnerability of Chemoresistant Hepatoblastoma.Cancers · 2022Article
- Minichromosome maintenance 2 is an independent predictor of survival in patients with lung adenocarcinoma.Molecular and clinical oncology · 2022Article
- DNA Replication Licensing Factors: Novel Targets for Cancer Therapy via Inhibiting the Stemness of Cancer Cells.International journal of biological sciences · 2022Review
- Expression Profile and Prognostic Values of Mini-Chromosome Maintenance Families (MCMs) in Breast Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Article
- Myc and the Replicative CMG Helicase: The Creation and Destruction of Cancer: Myc Over-Activation of CMG Helicases Drives Tumorigenesis and Creates a Vulnerability in CMGs for Therapeutic Intervention.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Review
- Mitotic DNA Synthesis Is Differentially Regulated between Cancer and Noncancerous Cells.Molecular cancer research : MCR · 2019Article
- Myc-driven chromatin accessibility regulates Cdc45 assembly into CMG helicases.Communications biology · 2019Article
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- The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth.Cell death & disease · 2017Article
- MCM7 promotes cancer progression through cyclin D1-dependent signaling and serves as a prognostic marker for patients with hepatocellular carcinoma.Cell death & disease · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of innovative therapeutic approaches. Recent studies indicate that suppression of the MCM helicase may provide a novel means to sensitize cancer cells to chemotherapeutic agents that inhibit replicative fork progression. Mammalian cells assemble more MCM complexes on DNA than are required to start S-phase. The excess MCM complexes function as backup initiation sites under conditions of replicative stress. The current study provides definitive evidence that cosuppression of the excess/backup MCM complexes sensitizes PDAC tumor lines to both gemcitabine and 5-FU, leading to increased loss of proliferative capacity compared with drugs alone. This occurs because reduced MCM levels prevent efficient recovery of DNA replication in tumor cells exposed to drug. PDAC tumor cells are more sensitive to MCM loss in the presence of gemcitabine than are nontumor, immortalized epithelial cells. Similarly, colon tumor cells are rendered less viable when cosuppression of MCM complexes occurs during exposure to the crosslinking agent oxaliplatin or topoisomerase inhibitor etoposide. IMPLICATIONS: These studies demonstrate that suppressing the backup complement of MCM complexes provides an effective sensitizing approach with the potential to increase the therapeutic index of drugs used in the clinical management of PDAC and other cancers.
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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.