title: Critical role of ABCG2 in ALA-photodynamic diagnosis and therapy of human brain tumor.
abstract: Primary brain tumors occur in around 250,000 people per year globally. Survival rates in primary brain tumors depend on the type of tumor, patient's age, the extent of surgical tumor removal, and other factors. Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma and meningiomas, whereas clinical application of photodynamic therapy (PDT) to brain tumor therapy has just recently started. Both PDD and PDT are achieved by a photon-induced physicochemical reaction, which is induced by the excitation of porphyrins exposed to light. In fluorescence-guided gross-total resection, PDD can be achieved by the administration of 5-aminolevulinic acid (5-ALA) as the precursor of protoporphyrin IX (PpIX). Exogenously administered ALA induces biosynthesis and accumulation of PpIX, a natural photosensitizer, in cancer cells. However, ATP-binding cassette transporter ABCG2 plays a critical role in regulating the cellular accumulation of porphyrins in cancer cells and thereby its expression and function can affect the efficacy of PDD and PDT. In response to the photoreaction of porphyrins leading to oxidative stress, the nuclear factor erythroid-derived 2-related transcription factor can transcriptionally upregulate ABCG2, which may reduce the efficacy of PDD and PDT. On the other hand, certain protein kinase inhibitors potentially enhance the efficacy of PDD and PDT by blocking ABCG2-mediated porphyrin efflux from cancer cells. In this context, it is of great interest to develop ABCG2 inhibitors that can be applied to PDD or PDT for the therapy of brain tumor and other tumors.
authors: NGO Personalized Medicine & Healthcare, Yokohama, Japan; Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan. Electronic address: toshihisa.ishikawa.r@gmail.com.
authors: Toshihisa
authors: T
authors: Ishikawa
authors: Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan.
authors: Yoshinaga
authors: Y
authors: Kajimoto
authors: Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University, Tokyo, Japan.
authors: Yutaka
authors: Y
authors: Inoue
authors: Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University, Tokyo, Japan.
authors: Yoji
authors: Y
authors: Ikegami
authors: Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan.
authors: Toshihiko
authors: T
authors: Kuroiwa
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001692:Biological Transport; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D000077156:Gefitinib; D006801:Humans; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000096:biosynthesis / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011524:Protoporphyrins / Q000096:biosynthesis; D011799:Quinazolines / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D011166:Porphyrins; D047428:Protein Kinase Inhibitors; D011524:Protoporphyrins; D011799:Quinazolines; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D000077156:Gefitinib
keywords: ABCG2; Brain tumor; Gliobastoma; Nrf2; Photodynamic diagnosis; Photodynamic therapy; Porphyrin