ArticleNeoplasia (New York, N.Y.)2013
Flavopiridol synergizes with sorafenib to induce cytotoxicity and potentiate antitumorigenic activity in EGFR/HER-2 and mutant RAS/RAF breast cancer model systems.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
18 citing papers in PubMed, 37 citations in OpenAlex.
- Intraline genomic heterogeneity of the triple-negative breast cancer MDA-MB-231-luc-GFP cell line.Computational and structural biotechnology journal · 2025Article
- The Pharmacological Implications of Flavopiridol: An Updated Overview.Molecules (Basel, Switzerland) · 2023Review
- B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis.Breast cancer research and treatment · 2022Article
- Review
- Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action.International journal of molecular sciences · 2021Review
- Regulation and New Treatment Strategies in Breast Cancer.Journal of life sciences (Westlake Village, Calif.) · 2019Article
- Flavonoids: New Frontier for Immuno-Regulation and Breast Cancer Control.Antioxidants (Basel, Switzerland) · 2019Review
- Sorafenib improves alkylating therapy by blocking induced inflammation, invasion and angiogenesis in breast cancer cells.Cancer letters · 2018Article
- Combined targeting of Raf and Mek synergistically inhibits tumorigenesis in triple negative breast cancer model systems.Oncotarget · 2017Article
- Article
- Radionuclide therapy using ¹³¹I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression.Journal of cancer research and clinical oncology · 2016Article
- Hyperactive ERK and persistent mTOR signaling characterize vemurafenib resistance in papillary thyroid cancer cells.Oncotarget · 2016Article
- A Versatile Cell Death Screening Assay Using Dye-Stained Cells and Multivariate Image Analysis.Assay and drug development technologies · 2015Article
- Cyclin-dependent kinase 11(p110) (CDK11(p110)) is crucial for human breast cancer cell proliferation and growth.Scientific reports · 2015Article
- Rapid detection of genetic mutations in individual breast cancer patients by next-generation DNA sequencing.Human genomics · 2015Article
- CDK/CCN and CDKI alterations for cancer prognosis and therapeutic predictivity.BioMed research international · 2014Review
- Inhibition of CDK-mediated phosphorylation of Smad3 results in decreased oncogenesis in triple negative breast cancer cells.Cell cycle (Georgetown, Tex.) · 2014Article
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Oncogenic receptor tyrosine kinase (RTK) signaling through the Ras-Raf-Mek-Erk (Ras-MAPK) pathway is implicated in a wide array of carcinomas, including those of the breast. The cyclin-dependent kinases (CDKs) are implicated in regulating proliferative and survival signaling downstream of this pathway. Here, we show that CDK inhibitors exhibit an order of magnitude greater cytotoxic potency than a suite of inhibitors targeting RTK and Ras-MAPK signaling in cell lines representative of clinically recognized breast cancer (BC) subtypes. Drug combination studies show that the pan-CDK inhibitor, flavopiridol (FPD), synergistically potentiated cytotoxicity induced by the Raf inhibitor, sorafenib (SFN). This synergy was most pronounced at sub-EC50 SFN concentrations in MDA-MB-231 (KRAS-G13D and BRAF-G464V mutations), MDA-MB-468 [epidermal growth factor receptor (EGFR) overexpression], and SKBR3 [ErbB2/EGFR2 (HER-2) overexpression] cells but not in hormone-dependent MCF-7 and T47D cells. Potentiation of SFN cytotoxicity by FPD correlated with enhanced apoptosis, suppression of retinoblastoma (Rb) signaling, and reduced Mcl-1 expression. SFN and FPD were also tested in an MDA-MB-231 mammary fat pad engraftment model of tumorigenesis. Mice treated with both drugs exhibited reduced primary tumor growth rates and metastatic tumor load in the lungs compared to treatment with either drug alone, and this correlated with greater reductions in Rb signaling and Mcl-1 expression in resected tumors. These findings support the development of CDK and Raf co-targeting strategies in EGFR/HER-2-overexpressing or RAS/RAF mutant BCs.
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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.