ArticleBritish journal of cancer2019
Systemic MEK inhibition enhances the efficacy of 5-aminolevulinic acid-photodynamic therapy.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- 6-Aminonicotinamide enhances the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy for neuroblastoma.BMC cancer · 2025Article
- Successful Treatment of MEK Inhibitor-Induced Paronychia in Neurofibromatosis with Photodynamic Therapy: A Case Report and Review of the Therapeutic Options.Journal of clinical medicine · 2025Article
- Comparison of the anti-cancer activity of 5-aminolevulinic acid-mediated photodynamic therapy after continuous wave and pulse irradiation in different histological types of canine mammary sarcoma tumors.Lasers in medical science · 2023Article
- Inflammatory cell death induced by 5-aminolevulinic acid-photodynamic therapy initiates anticancer immunity.Frontiers in oncology · 2023Article
- Detection of Canine Urothelial Carcinoma Cells in Urine Using 5-Aminolevulinic Acid.Animals : an open access journal from MDPI · 2022Article
- Methods to Measure the Inhibition of ABCG2 Transporter and Ferrochelatase Activity to Enhance Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Tumor Detection and Resection.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Assessment of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy on Bone Metastases: An in Vitro Study.Biology · 2021Article
- Key transporters leading to specific protoporphyrin IX accumulation in cancer cell following administration of aminolevulinic acid in photodynamic therapy/diagnosis.International journal of clinical oncology · 2021Review
- MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes.Scientific reports · 2020Article
- Photodynamic Therapy Using a Novel Phosphorus Tetraphenylporphyrin Induces an Anticancer Effect via Bax/Bcl-xL-related Mitochondrial Apoptosis in Biliary Cancer Cells.Acta histochemica et cytochemica · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProtoporphyrin IX (PpIX) gets accumulated preferentially in 5-aminolevulinic acid (5-ALA)-treated cancer cells. Photodynamic therapy (PDT) utilises the accumulated PpIX to trigger cell death by light-induced generation of reactive oxygen species (ROS). We previously demonstrated that oncogenic Ras/MEK decreases PpIX accumulation in cancer cells. Here, we investigated whether combined therapy with a MEK inhibitor would improve 5-ALA-PDT efficacy.
methodsCancer cells and mice models of cancer were treated with 5-ALA-PDT, MEK inhibitor or both MEK inhibitor and 5-ALA-PDT, and treatment efficacies were evaluated.
resultsRas/MEK negatively regulates the cellular sensitivity to 5-ALA-PDT as cancer cells pre-treated with a MEK inhibitor were killed more efficiently by 5-ALA-PDT. MEK inhibition promoted 5-ALA-PDT-induced ROS generation and programmed cell death. Furthermore, the combination of 5-ALA-PDT and a systemic MEK inhibitor significantly suppressed tumour growth compared with either monotherapy in mouse models of cancer. Remarkably, 44% of mice bearing human colon tumours showed a complete response with the combined treatment.
conclusionWe demonstrate a novel strategy to promote 5-ALA-PDT efficacy by targeting a cell signalling pathway regulating its sensitivity. This preclinical study provides a strong basis for utilising MEK inhibitors, which are approved for treating cancers, to enhance 5-ALA-PDT efficacy in the clinic.
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