ArticlePloS one2012
Synergistic effects of combined Wnt/KRAS inhibition in colorectal cancer cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 49 citations in OpenAlex.
- Targeting JOSD2 degrades β-catenin to suppress colorectal cancer metastasis by disrupting RAS/ERK/β-catenin axis.Acta pharmacologica Sinica · 2026Article
- Palbociclib targets β-catenin for degradation and synergizes with KRAS or ERK5 inhibition in colorectal cancer preclinical models.Journal of translational medicine · 2026Article
- CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review).International journal of oncology · 2026Review
- Review
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.The Journal of clinical investigation · 2025Article
- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.British journal of cancer · 2024Article
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.Gastroenterology · 2024Article
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Novel Insights into the Role of Kras in Myeloid Differentiation: Engaging with Wnt/β-Catenin Signaling.Cells · 2023Review
- Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug.Biomedicines · 2022Review
- Small-Molecule RAS Inhibitors as Anticancer Agents: Discovery, Development, and Mechanistic Studies.International journal of molecular sciences · 2022Review
- Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities.Signal transduction and targeted therapy · 2022Review
- Morindone from Morinda citrifolia as a potential antiproliferative agent against colorectal cancer cell lines.PloS one · 2022Article
- Synergistic Drug Combinations Prevent Resistance in ALK+ Anaplastic Large Cell Lymphoma.Cancers · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of Wnt signalling due to inability to degrade β-catenin is found in >85% of colorectal cancers. Approximately half of colon cancers express a constitutively active KRAS protein. A significant fraction of patients show both abnormalities. We previously reported that simultaneous down-regulation of both β-catenin and KRAS was necessary to induce significant cell death and tumor growth inhibition of colorectal cancer cells. Although attractive, an RNAi-based therapeutic approach is still far from being employed in the clinical setting. Therefore, we sought to recapitulate our previous findings by the use of small-molecule inhibitors of β-catenin and KRAS. We show here that the β-catenin inhibitors PKF115-584 and pyrvinium pamoate block β-catenin-dependent transcriptional activity and synergize with the KRAS inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS, salirasib) in colon cancer cells driven by Wnt and KRAS oncogenic signals, but not in cells carrying BRAF mutations. The combined use of these compounds was superior to the use of any drug alone in inducing cell growth arrest, cell death, MYC and survivin down-modulation, and inhibition of anchorage-independent growth. Expression analysis of selected cancer-relevant genes revealed down-regulation of CD44 as a common response to the combined treatments. These data provide a proof of principle for a combination therapeutic strategy in colorectal cancer.
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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.