ArticleBritish journal of cancer2017
Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 76 citations in OpenAlex.
- Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.Cancer medicine · 2023Trial
- Growth factor receptors IGF-1R and VEGFR2 are associated with the prognosis of patients with esophageal cancer after esophagectomy.Open life sciences · 2026Article
- Recent clinical advances in nonconjugated antibodies and antibody-drug conjugates for colorectal cancer treatment.Cancer cell international · 2025Review
- Insulin‑like growth factor in cancer: New perspectives (Review).Molecular medicine reports · 2025Review
- Picropodophyllin, an IGF‑1 receptor inhibitor, enhances oxaliplatin efficacy in chemoresistant colorectal cancer HCT116 cells by reducing metastatic potential.Oncology letters · 2025Article
- Advances in Targeted and Chemotherapeutic Strategies for Colorectal Cancer: Current Insights and Future Directions.Biomedicines · 2025Review
- A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer.Pharmacological reports : PR · 2025Review
- Comprehensive review of the resistance mechanisms of colorectal cancer classified by therapy type.Frontiers in immunology · 2025Review
- Advances in the role of membrane-bound transcription factors in carcinogenesis and therapy.Discover oncology · 2024Review
- Pharmacological agents targeting drug-tolerant persister cells in cancer.Pharmacological research · 2024Review
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
- The IGF1 Signaling Pathway: From Basic Concepts to Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- IGF1R-phosphorylated PYCR1 facilitates ELK4 transcriptional activity and sustains tumor growth under hypoxia.Nature communications · 2023Article
- Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.World journal of gastroenterology · 2023Review
- Insulin‑like growth factor axis: A potential nanotherapy target for resistant cervical cancer tumors (Review).Oncology letters · 2023Review
- Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia.International journal of molecular sciences · 2023Review
- A novel strategy for precise prognosis management and treatment option in colon adenocarcinoma with TP53 mutations.Frontiers in surgery · 2023Article
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Inhibition of insulin-like growth factor-1 receptor enhances eribulin-induced DNA damage in colorectal cancer.Cancer science · 2022Article
- Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients?International journal of molecular sciences · 2022Review
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Authors and funding
29 authors at 16 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving.
methodsWe analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients. The effect of IGF-1R activation and distribution was also assessed using cellular models of CRC and RNAi for functional validation.
resultsNuclear IGF-1R increased in metastatic tumours compared to paired untreated primary tumours, and significantly correlated with poor overall survival in mCRC patients. In vitro, chemo-resistant cell lines presented significantly higher levels of IGF-1R expression within the nuclear compartment, and PIAS3, a protein implicated also in the sumoylation process of intranuclear proteins, contributed to IGF-1R nuclear sequestration, highlighting the essential role of PIAS3 in this process. Intriguingly, we observed that ganitumab, an IGF-1R blocking-antibody used in several clinical trials, and dasatinib, an SRC inhibitor, increased the nuclear localisation of IGF-1R.
conclusionsOur study demonstrates that IGF-1R nuclear location might lead to chemotherapy and targeted agent resistance.
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