ArticleCancers2020
Tetraploidy-Associated Genetic Heterogeneity Confers Chemo-Radiotherapy Resistance to Colorectal Cancer Cells.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 25 citations in OpenAlex.
- Oxidative stress and serum deprivation influence the evolution of newly formed tetraploid cells during tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell and Nuclear Size Is Associated with Chromosomal Instability and Tumorigenicity in Cancer Cells That Undergo Whole Genome Doubling.Cancer research · 2026Article
- Copy number alteration fingerprint predicts the clinical response of oxaliplatin-based chemotherapy in metastatic colorectal cancer.NPJ precision oncology · 2026Article
- Transcriptomic and Cytogenetic Analysis of Oxaliplatin-Resistant Colorectal Adenocarcinoma HCT116 Cells to Identify Markers Associated with Platinum Resistance.International journal of molecular sciences · 2025Article
- In situ phenotypic and karyotypic co-detection of aneuploid TCs and TECs in cytological specimens with abnormal cervical screening results.BMC cancer · 2025Article
- JNK Inhibition Overcomes Resistance of Metastatic Tetraploid Cancer Cells to Irradiation-Induced Apoptosis.International journal of molecular sciences · 2025Article
- Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Morphological and Immunocytochemical Characterization of Paclitaxel-Induced Microcells in Sk-Mel-28 Melanoma Cells.Biomedicines · 2024Article
- Long noncoding RNA,Frontiers in cell and developmental biology · 2024Article
- Whole-genome doubling in tissues and tumors.Trends in genetics : TIG · 2023Review
- miR-186 induces tetraploidy in arsenic exposed human keratinocytes.Ecotoxicology and environmental safety · 2023Article
- Disruption of Multiple Overlapping Functions Following Stepwise Inactivation of the Extended Myc Network.Cells · 2022Article
- Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Review
- Context-dependent effects of whole-genome duplication during mammary tumor recurrence.Scientific reports · 2021Article
- Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment.Genes · 2021Review
- Regulation of signal transduction pathways in colorectal cancer: implications for therapeutic resistance.PeerJ · 2021Article
- Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer.Frontiers in oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Tetraploidy, or whole-genome duplication, is a common phenomenon in cancer and preludes chromosome instability, which strongly correlates with disease progression, metastasis, and treatment failure. Therefore, it is reasonable to hypothesize that tetraploidization confers multidrug resistance. Nevertheless, the contribution of whole-genome duplication to chemo-radiotherapy resistance remains unclear. Here, using isogenic diploid and near-tetraploid clones from three colorectal cancer cell lines and one non-transformed human epithelial cell line, we show a consistent growth impairment but a divergent tumorigenic potential of near-tetraploid cells. Next, we assessed the effects of first-line chemotherapeutic drugs, other commonly used agents and ionizing radiation, and found that whole-genome duplication promoted increased chemotherapy resistance and also conferred protection against irradiation. When testing the activation of apoptosis, we observed that tetraploid cells were less prone to caspase 3 activation after treatment with first-line chemotherapeutic agents. Furthermore, we found that pre-treatment with ataxia telangiectasia and Rad3 related (ATR) inhibitors, which targets response to replication stress, significantly enhanced the sensitivity of tetraploid cells to first-line chemotherapeutic agents as well as to ionizing radiation. Our findings provide further insight into how tetraploidy results in greater levels of tolerance to chemo-radiotherapeutic agents and, moreover, we show that ATR inhibitors can sensitize near-tetraploid cells to commonly used chemo-radiotherapy regimens.
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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.