ArticleBiomarker research2023
HMGA1 augments palbociclib efficacy via PI3K/mTOR signaling in intrahepatic cholangiocarcinoma.
Article in Biomarker research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 54 citations in OpenAlex.
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- Artificial neural network-based immune biomarker signature predicts pathological complete response to neoadjuvant chemotherapy in HER2-negative breast cancer.Frontiers in oncology · 2026Article
- mTOR signaling in cholangiocarcinoma: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- HMGA1 is associated with unfavorable outcome and accelerates the aggressiveness of cholangiocarcinoma.SAGE open medicine · 2026Article
- Development of CDK4/6 Inhibitors in Gastrointestinal Cancers: Biomarkers to Move Forward.Current issues in molecular biology · 2025Review
- High mobility group A1 (HMGA1) promotes esophageal squamous cell carcinoma progression by inhibiting STING-mediated anti-tumor immunity.Nature communications · 2025Article
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Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer that is challenging to diagnose at an early stage. Despite recent advances in combination chemotherapy, drug resistance limits the therapeutic value of this regimen. iCCA reportedly harbors high HMGA1 expression and pathway alterations, especially hyperactivation of the CCND1/CDK4/CDK6 and PI3K signaling pathway. In this study, we explored the potential of targeting CDK4/6 and PI3K inhibition to treat iCCA.
methodsThe significance of HMGA1 in iCCA was investigated with in vitro/vivo experiments. Western blot, qPCR, dual-luciferase reporter and immunofluorescence assays were performed to examine the mechanism of HMGA1 induced CCND1 expression. CCK-8, western blot, transwell, 3D sphere formation and colony formation assays were conducted to predict the potential role of CDK4/6 inhibitors PI3K/mTOR inhibitors in iCCA treatment. Xenograft mouse models were also used to determine the efficacy of combination treatment strategies related to HMGA1 in iCCA.
resultsHMGA1 promoted the proliferation, epithelial-mesenchymaltransition (EMT), metastasis and stemness of iCCA. In vitro studies showed that HMGA1 induced CCND1 expression via promoting CCND1 transcription and activating the PI3K signaling pathway. Palbociclib(CDK4/6 inhibitor) could suppress iCCA proliferation, migration and invasion, especially during the first 3 days. Although there was more stable attenuation of growth in the HIBEpic model, we observed substantial outgrowth in each hepatobiliary cancer cell model. PF-04691502(PI3K/mTOR inhibitor) exhibited similar effects to palbociclib. Compared with monotherapy, the combination retained effective inhibition for iCCA through the more potent and steady inhibition of CCND1, CDK4/6 and PI3K pathway. Furthermore, more significant inhibition of the common downstream signaling pathways is observed with the combination compared to monotherapy.
conclusionsOur study reveals the potential therapeutic role of dual inhibition of CDK4/6 and PI3K/mTOR pathways in iCCA, and proposes a new paradigm for the clinical treatment of iCCA.
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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.