ArticleBiochemical pharmacology2022
Inhibition of ABCG2 transporter by lapatinib enhances 5-aminolevulinic acid-mediated protoporphyrin IX fluorescence and photodynamic therapy response in human glioma cell lines.
Article in Biochemical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 34 citations in OpenAlex.
- 5-ALA in Oncology: Current Clinical Applications, Biological Limitations, and Emerging Translational Strategies.Biomedicines · 2026Review
- Emerging uses of 5-aminolevulinic-acid-induced protoporphyrin IX in medicine: a review of multifaceted, ubiquitous, molecular diagnostic, therapeutic, and theranostic opportunities.Journal of biomedical optics · 2025Review
- Review
- 5-Aminolevulinic acid-mediated photodynamic therapy in combination with kinase inhibitor lapatinib enhances glioblastoma cell death.Apoptosis : an international journal on programmed cell death · 2024Article
- Hemin Promotes Higher Effectiveness of Aminolevulinic-Photodynamic Therapy (ALA-PDT) in A549 Lung Cancer Cell Line by Interrupting ABCG2 Expression.Medical sciences (Basel, Switzerland) · 2024Article
- Determinants of Photodynamic Therapy Resistance in Cancer Cells.International journal of molecular sciences · 2024Review
- Roles of the ABCG2 Transporter in Protoporphyrin IX Distribution and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Molecular Determinants for Photodynamic Therapy Resistance and Improved Photosensitizer Delivery in Glioma.International journal of molecular sciences · 2024Review
- Current Photodynamic Therapy for Glioma Treatment: An Update.Biomedicines · 2024Review
- Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.Journal of biomedical optics · 2024Article
- Screening of photosensitizers-ATP binding cassette (ABC) transporter interactionsCancer drug resistance (Alhambra, Calif.) · 2024Article
- 5-aminolevulinic acid induced photodynamic reactions in diagnosis and therapy for female lower genital tract diseases.Frontiers in medicine · 2024Review
- Nanoparticles drug delivery for 5-aminolevulinic acid (5-ALA) in photodynamic therapy (PDT) for multiple cancer treatment: a critical review on biosynthesis, detection, and therapeutic applications.Journal of cancer research and clinical oncology · 2023Review
- Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro.Pharmaceutics · 2023Article
- Targeting ABCG2 transporter to enhance 5-aminolevulinic acid for tumor visualization and photodynamic therapy.Biochemical pharmacology · 2023Review
- Epigenetic profiling reveals a strong association between lack of 5-ALA fluorescence andNeuro-oncology practice · 2023Article
- Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment.Molecules (Basel, Switzerland) · 2023Article
- 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy.Bioengineering (Basel, Switzerland) · 2023Review
- Photodynamic therapy and associated targeting methods for treatment of brain cancer.Frontiers in pharmacology · 2023Review
- Amplifying the efficacy of ALA-based prodrugs for photodynamic therapy using nanotechnology.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
5-Aminolevulinic acid (ALA) is an intraoperative molecular probe approved for fluorescence-guided resection (FGR) of high-grade gliomas to achieve maximal safe tumor resection. Although ALA has no fluorescence on its own, it is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) with red fluorescence for tumor detection and photosensitizing activity for photodynamic therapy (PDT). The preferential tumor accumulation of PpIX following ALA administration enables the use of ALA as a prodrug for PpIX FGR and PDT of gliomas. Since intracellular PpIX in tumor cells after ALA treatment is influenced by biological processes including PpIX bioconversion catalyzed by ferrochelatase (FECH) and PpIX efflux by ATP-binding cassette subfamily G member 2 (ABCG2), we determined the activity of FECH and ABCG2 in a panel of human glioma cell lines and correlated with intracellular and extracellular PpIX levels and PDT response. We found that glioma cell lines with ABCG2 activity exhibited the trend of low intracellular PpIX, high extracellular PpIX and low PDT response, whereas no particular correlation was seen with FECH activity. Inhibition of PpIX efflux with ABCG2 inhibitors was more effective in enhancing ALA-PpIX fluorescence and PDT response than blocking PpIX bioconversion with iron chelator deferoxamine. We also showed that a clinically used kinase inhibitor lapatinib could be repurposed for therapeutic enhancement of ALA due to its potent ABCG2 inhibitory activity. Our study reveals ABCG2 as an important biological determinant of PpIX fluorescence in glioma cells and suggests ABCG2 inhibition with lapatinib as a promising therapeutic enhancement approach.
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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.