ArticleOncotarget2015
A MEK/PI3K/HDAC inhibitor combination therapy for KRAS mutant pancreatic 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 28 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
28 citing papers in PubMed, 42 citations in OpenAlex.
- The Dual Role ofBiology · 2025Review
- PPARδ Orchestrates a Prometastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer.Cancer research · 2025Article
- Review
- Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment.Cancers · 2022Review
- Targeting KRAS in PDAC: A New Way to Cure It?Cancers · 2022Review
- Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy.Molecules (Basel, Switzerland) · 2021Review
- Clinical Utility of Epigenetic Changes in Pancreatic Adenocarcinoma.Epigenomes · 2021Review
- Dual Inhibition of Histone Deacetylases and the Mechanistic Target of Rapamycin Promotes Apoptosis in Cell Line Models of Uveal Melanoma.Investigative ophthalmology & visual science · 2021Article
- LPIN1 downregulation enhances anticancer activity of the novel HDAC/PI3K dual inhibitor FK-A11.Cancer science · 2021Article
- Combination of KRAS gene silencing and PI3K inhibition for ovarian cancer treatment.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Exploiting the relevance of CA 19-9 in pancreatic cancer.Journal of cancer metastasis and treatment · 2020Article
- CEP164 Deficiency Causes Hyperproliferation of Pancreatic Cancer Cells.Frontiers in cell and developmental biology · 2020Article
- Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches.Radiation oncology (London, England) · 2019Review
- Synergistic inhibition of MEK and reciprocal feedback networks for targeted intervention in malignancy.Cancer biology & medicine · 2019Article
- Combination treatment strategy for pancreatic cancer involving the novel HDAC inhibitor MPT0E028 with a MEK inhibitor beyond K-Ras status.Clinical epigenetics · 2019Article
- Targeting mitochondrial hexokinases increases efficacy of histone deacetylase inhibitors in solid tumor models.Experimental cell research · 2019Article
- STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis.Genes & development · 2018Article
- Antitumor activity of the novel HDAC inhibitor CUDC-101 combined with gemcitabine in pancreatic cancer.American journal of cancer research · 2018Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
- Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, metastatic disease with limited treatment options. Factors contributing to the metastatic predisposition and therapy resistance in pancreatic cancer are not well understood. Here, we used a mouse model of KRAS-driven pancreatic carcinogenesis to define distinct subtypes of PDAC metastasis: epithelial, mesenchymal and quasi-mesenchymal. We examined pro-survival signals in these cells and the therapeutic response differences between them. Our data indicate that the initiation and maintenance of the transformed state are separable, and that KRAS dependency is not a fundamental constant of KRAS-initiated tumors. Moreover, some cancer cells can shuttle between the KRAS dependent (drug-sensitive) and independent (drug-tolerant) states and thus escape extinction. We further demonstrate that inhibition of KRAS signaling alone via co-targeting the MAPK and PI3K pathways fails to induce extensive tumor cell death and, therefore, has limited efficacy against PDAC. However, the addition of histone deacetylase (HDAC) inhibitors greatly improves outcomes, reduces the self-renewal of cancer cells, and blocks cancer metastasis in vivo. Our results suggest that targeting HDACs in combination with KRAS or its effector pathways provides an effective strategy for the treatment of PDAC.
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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.