ArticleOncotarget2014
Targeting the DNA replication checkpoint by pharmacologic inhibition of Chk1 kinase: a strategy to sensitize APC mutant colon cancer cells to 5-fluorouracil chemotherapy.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Article
- A panorama of colon cancer in the era of liquid biopsy.The journal of liquid biopsy · 2024Review
- MiRZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- BMX, a specific HDAC8 inhibitor, with TMZ for advanced CRC therapy: a novel synergic effect to elicit p53-, β-catenin- and MGMT-dependent apoptotic cell death.Cell communication and signaling : CCS · 2022Article
- Transcriptome Analysis of the Anti-Proliferative Effects of Ginsenoside Rh3 on HCT116 Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Review
- ERCC1, PARP-1, and AQP1 as predictive biomarkers in colon cancer patients receiving adjuvant chemotherapy.Cancer biomarkers : section A of Disease markers · 2020Article
- Synergy of Ginkgetin and Resveratrol in Suppressing VEGF-Induced Angiogenesis: A Therapy in Treating Colorectal Cancer.Cancers · 2019Article
- ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.European journal of medicinal chemistry · 2019Article
- Individualized predictive signatures for 5-fluorouracil-based chemotherapy in right- and left-sided colon cancer.Cancer science · 2018Article
- Therapeutic strategies against cancer stem cells in human colorectal cancer.Oncology letters · 2017Article
- Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Article
- NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.Oncotarget · 2017Article
- Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy.Oncotarget · 2017Article
- StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.Cancer medicine · 2017Article
- Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients.Oncotarget · 2016Article
- Interaction between APC and Fen1 during breast carcinogenesis.DNA repair · 2016Review
- APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane.Molecular biology of the cell · 2016Article
- Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer.World journal of gastrointestinal oncology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-fluorouracil (5-FU) is the first line component used in colorectal cancer (CRC) therapy however even in combination with other chemotherapeutic drugs recurrence is common. Mutations of the adenomatous polyposis coli (APC) gene are considered as the initiating step of transformation in familial and sporadic CRCs. We have previously shown that APC regulates the cellular response to DNA replication stress and recently hypothesized that APC mutations might therefore influence 5-FU resistance. To test this, we compared CRC cell lines and show that those expressing truncated APC exhibit a limited response to 5-FU and arrest in G1/S-phase without undergoing lethal damage, unlike cells expressing wild-type APC. In SW480 APC-mutant CRC cells, 5-FU-dependent apoptosis was restored after transient expression of full length APC, indicating a direct link between APC and drug response. Furthermore, we could increase sensitivity of APC truncated cells to 5-FU by inactivating the Chk1 kinase using drug treatment or siRNA-mediated knockdown. Our findings identify mutant APC as a potential tumor biomarker of resistance to 5-FU, and importantly we show that APC-mutant CRC cells can be made more sensitive to 5-FU by use of Chk1 inhibitors.
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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.