ArticleFrontiers in oncology2022
Patient Derived Organoids Confirm That PI3K/AKT Signalling Is an Escape Pathway for Radioresistance and a Target for Therapy in Rectal Cancer.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 24 citations in OpenAlex.
- Organoids in Precision Radiotherapy: Methodological Foundations, Tumor-Specific Evidence, and Translational Roadmaps.Cancer medicine · 2026Review
- From bench to bedside: advancing our understanding of radioresistance in rectal cancer.Cancer metastasis reviews · 2026Review
- Organoids in cancer therapy: translational applications and clinical promise.Molecular cancer · 2026Review
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Overcoming the Challenge: A Comprehensive Review of Neoadjuvant Treatment Resistance in Rectal Cancer.Journal of gastrointestinal cancer · 2025Review
- Identification and modulation of a PI3K/AKT/mTOR pathway-targeting microRNA in order to increase colorectal cancer cells radiosensitivity in vitro.BMC cancer · 2025Article
- Integrating Tumor and Organoid DNA Methylation Profiles Reveals Robust Predictors of Chemotherapy Response in Rectal Cancer.medRxiv : the preprint server for health sciences · 2025Article
- PTEN and P-4E-BP1 might be associated with postoperative recurrence of rectal cancer patients undergoing concurrent radiochemotherapy.BMC cancer · 2024Article
- ST6GAL1 is associated with poor response to chemoradiation in rectal cancer.Neoplasia (New York, N.Y.) · 2024Article
- Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.Expert reviews in molecular medicine · 2024Review
- Intra-promoter switch of transcription initiation sites in proliferation signaling-dependent RNA metabolism.Nature structural & molecular biology · 2023Article
- PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer.Cell death & disease · 2023Article
- PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection.Science (New York, N.Y.) · 2023Article
- Exploring New Dimensions of Tumor Heterogeneity: The Application of Single Cell Analysis to Organoid-Based 3D In Vitro Models.Advanced healthcare materials · 2023Review
- Standard: Human intestinal cancer organoids.Cell regeneration (London, England) · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objectives: Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. We aimed to understand the mechanisms of resistance to chemoradiotherapy in rectal cancer using patient derived organoid models. Design: To understand the mechanisms underlying this resistance, we compared the pre-treatment transcriptomes of patient-derived organoids (PDO) with measured radiotherapy sensitivity to identify biological pathways involved in radiation resistance coupled with single cell sequencing, genome wide CRISPR-Cas9 and targeted drug screens. Results: RNA sequencing enrichment analysis revealed upregulation of PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes in radioresistant PDOs. Single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 and PI3K/AKT upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. We then tested the efficiency of dual PI3K/mTOR inhibitors in improving cancer cell sensitivity to radiotherapy. After irradiation, significant AKT phosphorylation was detected ( Conclusions: The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its targeted pharmacological inhibition leads to significant radiosensitisation in CRC organoids, making it a potential target for clinical trials.
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