ArticleCell death & disease2021
Alpelisib combination treatment as novel targeted therapy against hepatocellular carcinoma.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- GSH-Responsive Nanoparticles Enhance Hepatocellular Carcinoma Immunotherapy Through Synergistic Effects of Cuproptosis and PI3K Inhibitor Combination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Annexin A3 potentiates lenvatinib resistance in hepatocellular carcinoma through multiple approaches amplified by a positive feedback loop.Cell death & disease · 2026Article
- STOML2 promotes hepatocellular carcinoma cell proliferation, invasion and migration by activating the PI3K/AKT signaling pathway (Review).Oncology letters · 2026Review
- Molecular classification and construction of prognostic risk model via machine learning based on metabolic-related genes in hepatocellular carcinoma.Translational cancer research · 2026Article
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- Harnessing Single-Cell RNA-Seq for Computational Drug Repurposing in Cancer Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids.SLAS discovery : advancing life sciences R & D · 2025Article
- FGFR1 overexpression promotes resistance to PI3K inhibitor alpelisib in luminal breast cancer cells through receptor tyrosine kinase signaling-mediated activation of the estrogen receptor.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Cytoglobin suppresses oxidative damage and compensatory proliferation via inhibiting AKT/ERK1/2/CyclinD1 axis in hepatocellular carcinoma.American journal of cancer research · 2025Article
- The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Exercise-related immune gene signature for hepatocellular carcinoma: machine learning and multi-omics analysis.Frontiers in immunology · 2025Article
- Preclinical Models of Hepatocellular Carcinoma: Current Utility, Limitations, and Challenges.Biomedicines · 2024Review
- β1 integrin mediates unresponsiveness to PI3Kα inhibition for radiochemosensitization of 3D HNSCC models.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- The essential roles of lncRNAs/PI3K/AKT axis in gastrointestinal tumors.Frontiers in cell and developmental biology · 2024Review
- mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation.Frontiers in oncology · 2024Review
- Constructed Risk Prognosis Model Associated with Disulfidptosis lncRNAs in HCC.International journal of molecular sciences · 2023Article
- RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro.International journal of molecular sciences · 2023Article
- Synthetic Vulnerabilities in the KRAS Pathway.Cancers · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary cancer with an unsatisfactory long-term survival. Gain of function mutations of PIK3CA occur in a subset of human HCC. Alpelisib, a selective PIK3CA inhibitor, has been approved by the FDA to treat PIK3CA mutant breast cancers. In this manuscript, we evaluated the therapeutic efficacy of alpelisib, either alone or in combination, for the treatment of HCC. We tested alpelisib in mouse HCC induced by hydrodynamic injection of c-Met/PIK3CA(H1047R) (c-Met/H1047R), c-Met/PIK3CA(E545K) (c-Met/E545K), and c-Met/sgPten gene combinations. Alpelisib slowed down the growth of c-Met/H1047R and c-Met/E545K HCC but was ineffective in c-Met/sgPten HCC. Mechanistically, alpelisib inhibited p-ERK and p-AKT in c-Met/H1047R and c-Met/E545K HCC progression but did not affect the mTOR pathway or genes involved in cell proliferation. In human HCC cell lines transfected with PIK3CA(H1047R), alpelisib synergized with the mTOR inhibitor MLN0128 or the CDK4/6 inhibitor palbociclib to suppress HCC cell growth. In c-Met/H1047R mice, alpelisib/MLN0128 or alpelisib/palbociclib combination therapy caused tumor regression. Our study demonstrates that alpelisib is effective for treating PIK3CA-mutated HCC by inhibiting MAPK and AKT cascades. Furthermore, combining alpelisib with mTOR or CDK4/6 inhibitors has a synergistic efficacy against PIK3CA-mutated HCC, providing novel opportunities for precision medicine against HCC.
Indexed as
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What Socratic holds
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 Socratic graph.