ArticleInternational journal of cancer2014
STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in vitro and in vivo.
Article in International journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 126 citations in OpenAlex.
- Targeting PRMT5 Inhibitor-Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam.Cancer research communications · 2026Article
- Effect of the miR‑26a/b‑5p‑STAT3‑YKL‑40 regulatory axis on proliferation, migration, and invasion of endometrial cancer cells.Oncology reports · 2026Article
- Targeting metabolic dependencies to reverse chemoradiotherapy resistance in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting STAT3 with SH-4-54 suppresses stemness and chemoresistance in cancer stem-like cells derived from colorectal cancer.World journal of clinical oncology · 2025Article
- Multi-omics analysis reveals the impact of YAP/TEAD4-mediated EIF5A1 expression on mitochondrial apoptosis and bladder cancer progression.BMC cancer · 2025Article
- Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.Current gene therapy · 2025Review
- Comprehensive review of the resistance mechanisms of colorectal cancer classified by therapy type.Frontiers in immunology · 2025Review
- STAT3 and the STAT3‑regulated inhibitor of apoptosis protein survivin as potential therapeutic targets in colorectal cancer (Review).Biomedical reports · 2024Review
- Improvement of Docetaxel Efficacy through Simultaneous Blockade of Transcription Factors NF-κB and STAT-3 Using Pentoxifylline and Stattic in Prostate Cancer Cells.Current issues in molecular biology · 2024Article
- Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.Expert reviews in molecular medicine · 2024Review
- Competitive endogenous RNA networks: Decoding the role of long non-coding RNAs and circular RNAs in colorectal cancer chemoresistance.Journal of cellular and molecular medicine · 2024Review
- Interplay of miRNAs and lncRNAs in STAT3 signaling pathway in colorectal cancer progression.Cancer cell international · 2024Review
- AUF1-induced circular RNA hsa_circ_0010467 promotes platinum resistance of ovarian cancer through miR-637/LIF/STAT3 axis.Cellular and molecular life sciences : CMLS · 2023Article
- Interrogating colorectal cancer metastasis to liver: a search for clinically viable compounds and mechanistic insights in colorectal cancer Patient Derived Organoids.Journal of experimental & clinical cancer research : CR · 2023Article
- Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells.Molecular cancer therapeutics · 2023Article
- Modulation of rectal cancer stemness, patient outcome and therapy response by adipokines.Journal of physiology and biochemistry · 2023Article
- Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.World journal of gastroenterology · 2023Review
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
- 5-Fluorouracil Combined with Rutaecarpine Synergistically Suppresses the Growth of Colon Cancer Cells by Inhibiting STAT3.Drug design, development and therapy · 2023Article
- Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway.International journal of oncology · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Increased activity of signal transducer and activator of transcription 3 (STAT3) is common in human malignancies, including colorectal cancers (CRCs). We have recently reported that STAT3 gene expression correlates with resistance of CRC cell lines to 5-fluorouracil (5-FU)-based chemoradiotherapy (CT/RT). This is of considerable clinical importance, because a large proportion of rectal cancers are resistant to preoperative multimodal treatment. To test whether STAT3 contributes to CT/RT-resistance, we first confirmed that STAT3 protein expression correlated positively with increasing resistance. While STAT3 was not constitutively active, stimulation with interleukin-6 (IL-6) resulted in remarkably higher expression levels of phosphorylated STAT3 in CT/RT-resistant cell lines. A similar result was observed when we determined IL-6-induced expression levels of phosphorylated STAT3 following irradiation. Next, STAT3 was inhibited in SW480 and SW837 using siRNA, shRNA and the small-molecule inhibitor STATTIC. Successful silencing and inhibition of phosphorylation was confirmed using Western blot analysis and a luciferase reporter assay. RNAi-mediated silencing as well as STATTIC treatment resulted in significantly decreased clonogenic survival following exposure to 3 µM of 5-FU and irradiation in a dose-dependent manner, with dose-modifying factors of 1.3-2.5 at a surviving fraction of 0.37. Finally, STAT3 inhibition led to a profound CT/RT-sensitization in a subcutaneous xenograft model, with a significantly delayed tumor regrowth in STATTIC-treated mice compared with control animals. These results highlight a potential role of STAT3 in mediating treatment resistance and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to CT/RT.
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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.