ArticleCancer biology & therapy2011
Sorafenib attenuates p21 in kidney cancer cells and augments cell death in combination with DNA-damaging chemotherapy.
Article in Cancer biology & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- Multiplexed P21/MCM-2 Detection Predicts Relapse and May Identify Tyrosine Kinase Inhibitor-Resistant Patients in Clear Cell Renal Cell Carcinoma.Cancer research communications · 2026Article
- Pro-survival roles for p21(Cip1/Waf1) in non-small cell lung cancer.British journal of cancer · 2025Article
- Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket.iScience · 2024Article
- CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences · 2023Review
- Targeting hyaluronic acid synthase-3 (HAS3) for the treatment of advanced renal cell carcinoma.Cancer cell international · 2022Article
- Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups.Biomolecules · 2022Review
- Sorafenib, rapamycin, and venetoclax attenuate doxorubicin-induced senescence and promote apoptosis in HCT116 cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- The cyclin dependent kinase inhibitor p21Frontiers in oncology · 2022Article
- RNA sequencing of long-term label-retaining colon cancer stem cells identifies novel regulators of quiescence.iScience · 2021Article
- Permutation-based identification of important biomarkers for complex diseases via machine learning models.Nature communications · 2021Article
- Synergistic Anticancer Activity ofInternational journal of molecular sciences · 2021Article
- Anti-Cancer Activity of PAK4/NAMPT Inhibitor and Programmed Cell Death Protein-1 Antibody in Kidney Cancer.Kidney360 · 2020Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- Article
- Casein Kinase 1 Delta Regulates Cell Proliferation, Response to Chemotherapy and Migration in Human Ovarian Cancer Cells.Frontiers in oncology · 2019Article
- 16-Hydroxycleroda-3,13-dien-15,16-olide induces anoikis in human renal cell carcinoma cells: involvement of focal adhesion disassembly and signaling.OncoTargets and therapy · 2018Article
- Anticystogenic activity of a small molecule PAK4 inhibitor may be a novel treatment for autosomal dominant polycystic kidney disease.Kidney international · 2017Article
- MDM2 Antagonists Counteract Drug-Induced DNA Damage.EBioMedicine · 2017Article
- Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.Oncotarget · 2017Article
- Synergistic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide and Sorafenib Against Cancer Stem Cells, Anaplastic Thyroid Cancer.Neoplasia (New York, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
There are few effective therapeutic options for metastatic renal cell carcinoma (RCC). Conventional chemotherapeutic agents are ineffective since these tumors are unusually resistant to DNA damage, likely due to an exuberant DNA repair response. Sorafenib, as one of the few available effective therapeutic options for metastatic RCC, has been shown to inhibit cell proliferation by inhibition of tyrosine kinases. We have recently shown that sorafenib inhibits soluble epoxide hydrolase, which catalyzes metabolism of the anti-inflammatory epoxyeicosatrienoic acids. Given previous work demonstrating the anti-apoptotic role of p21 in RCC as a potential mechanism for its drug resistance, we asked whether sorafenib signals through this pathway. We now show that sorafenib markedly decreases p21 levels in several RCC and hepatocellular carcinoma cells. Neither the MEK inhibitor PD98059 nor the sEH inhibitor t-AUCB, which represent known sorafenib-targeted signaling pathways, alter p21 levels, demonstrating that the p21 inhibitory effect of sorafenib is independent of these signaling cascades. In cells treated with doxorubicin to augment p21, sorafenib markedly decreases this protein, and the combinations of paclitaxel or doxorubicin with sorafenib show additive cytotoxicity as a function of the VHL status of the cells, suggesting that lower doses of each agent could be used in the clinical setting. In summary, we show a novel signaling pathway by which sorafenib exerts its salutary effects in RCC; future work will focus on the use of these drug combinations in the context of conventional therapeutics, and novel compounds and protocols targeting p21 in conjunction with sorafenib should be pursued.
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