ArticleOncotarget2015
The cytotoxic effects of regorafenib in combination with protein kinase D inhibition in human colorectal cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Overcoming Regorafenib Resistance in Colorectal Cancer: Synergistic Efficacy of Cilengitide in HT29 and WiDr Cells.Medeniyet medical journal · 2026Article
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Article
- Potential role for protein kinase D inhibitors in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Regorafenib and Ruthenium Complex Combination Inhibit Cancer Cell Growth by Targeting PI3K/AKT/ERK Signalling in Colorectal Cancer Cells.International journal of molecular sciences · 2022Article
- Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- A zebrafish forward genetic screen identifies an indispensable threonine residue in the kinase domain of PRKD2.Biology open · 2021Article
- Small-Molecule Inhibitor Targeting Protein Kinase D: A Potential Therapeutic Strategy.Frontiers in oncology · 2021Review
- Article
- A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo.Cell proliferation · 2018Article
- DNA damage and apoptosis induced by a potent orally podophyllotoxin derivative in breast cancer.Cell communication and signaling : CCS · 2018Article
- Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M.Cellular and molecular life sciences : CMLS · 2018Article
- A marginal anticancer effect of regorafenib on pancreatic carcinoma cells in vitro, ex vivo, and in vivo.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- XWL-1-48 exerts antitumor activity via targeting topoisomerase II and enhancing degradation of Mdm2 in human hepatocellular carcinoma.Scientific reports · 2017Article
- Inhibition of AKT/FoxO3a signaling induced PUMA expression in response to p53-independent cytotoxic effects of H1: A derivative of tetrandrine.Cancer biology & therapy · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Metastatic colorectal cancer (mCRC) remains a major public health problem, and diagnosis of metastatic disease is usually associated with poor prognosis. The multi-kinase inhibitor regorafenib was approved in 2013 in the U.S. for the treatment of mCRC patients who progressed after standard therapies. However, the clinical efficacy of regorafenib is quite limited. One potential strategy to improve mCRC therapy is to combine agents that target key cellular signaling pathways, which may lead to synergistic enhancement of antitumor efficacy and overcome cellular drug resistance. Protein kinase D (PKD), a family of serine/threonine kinases, mediates key signaling pathways implicated in multiple cellular processes. Herein, we evaluated the combination of regorafenib with a PKD inhibitor in several human CRC cells. Using the Chou-Talalay model, the combination index values for this combination treatment demonstrated synergistic effects on inhibition of cell proliferation and clonal formation. This drug combination resulted in induction of apoptosis as determined by flow cytometry, increased PARP cleavage, and decreased activation of the anti-apoptotic protein HSP27. This combination also yielded enhanced inhibition of ERK, AKT, and NF-κB signaling. Taken together, PKD inhibition in combination with regorafenib appears to be a promising strategy for the treatment of mCRC.
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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.