ArticleInternational journal of molecular sciences2018
Non-Coding Micro RNAs and Hypoxia-Inducible Factors Are Selenium Targets for Development of a Mechanism-Based Combination Strategy in Clear-Cell Renal Cell Carcinoma-Bench-to-Bedside Therapy.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis.Annals of medicine · 2026Pooled it
- Selenium compounds for cancer prevention and therapy - human clinical trial considerations.Medical review (2021) · 2025Review
- Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear-cell Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: Mechanisms and therapeutic potential.Cancer treatment and research communications · 2024Article
- Identification and verification of a novel anoikis-related gene signature with prognostic significance in clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Druggable Biomarkers Altered in Clear Cell Renal Cell Carcinoma: Strategy for the Development of Mechanism-Based Combination Therapy.International journal of molecular sciences · 2023Review
- Review
- MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets.International journal of molecular sciences · 2022Article
- Potential Role of Selenium in the Treatment of Cancer and Viral Infections.International journal of molecular sciences · 2022Review
- Review
- High expression of hypoxia inducible factor 1α related with acquired resistant to EGFR tyrosine kinase inhibitors in NSCLC.Scientific reports · 2021Article
- MicroRNA Profiling of Morphologically Heterogeneous Clear Cell Renal Cell Carcinoma.Journal of Cancer · 2021Article
- HIF-1α Induces HECTD2 Up-Regulation and Aggravates the Malignant Progression of Renal Cell CancerFrontiers in cell and developmental biology · 2021Article
- Article
- The interplay between HIF-1α and noncoding RNAs in cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Clinical significance of high expression of stanniocalcin-2 in hepatocellular carcinoma.Bioscience reports · 2019Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Durable response, inherent or acquired resistance, and dose-limiting toxicities continue to represent major barriers in the treatment of patients with advanced clear-cell renal cell carcinoma (ccRCC). The majority of ccRCC tumors are characterized by the loss of Von Hippel⁻Lindau tumor suppressor gene function, a stable expression of hypoxia-inducible factors 1α and 2α (HIFs), an altered expression of tumor-specific oncogenic microRNAs (miRNAs), a clear cytoplasm with dense lipid content, and overexpression of thymidine phosphorylase. The aim of this manuscript was to confirm that the downregulation of specific drug-resistant biomarkers deregulated in tumor cells by a defined dose and schedule of methylselenocysteine (MSC) or seleno-l-methionine (SLM) sensitizes tumor cells to mechanism-based drug combination. The inhibition of HIFs by selenium was necessary for optimal therapeutic benefit. Durable responses were achieved only when MSC was combined with sunitinib (a vascular endothelial growth factor receptor (VEGFR)-targeted biologic), topotecan (a topoisomerase 1 poison and HIF synthesis inhibitor), and S-1 (a 5-fluorouracil prodrug). The documented synergy was selenium dose- and schedule-dependent and associated with enhanced prolyl hydroxylase-dependent HIF degradation, stabilization of tumor vasculature, downregulation of 28 oncogenic miRNAs, as well as the upregulation of 12 tumor suppressor miRNAs. The preclinical results generated provided the rationale for the development of phase 1/2 clinical trials of SLM in sequential combination with axitinib in ccRCC patients refractory to standard therapies.
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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.