title: ["Vicious circles" of glioblastoma tumors: vascularization and invasiveness].
abstract: Glioblastoma multiforme is the most common and a particularly aggressive form of glial primary brain tumors. This malignancy accounts for ca. 70% of all diagnosed cases. Unfortunately, average survival of glioma patients does not exceed one year from diagnosis. Specific vascularization pattern (presence of numerous microvessels and glomerular vessels) and exceptional invasiveness are characteristic features of glioblastoma tumors. Both of these features reflect complex underlying processes forming two vicious circles. Common to both of these circles is the state of tumor underoxygenation. Hypoxia that occurs in the vicinity of abnormal tumor blood vessels stimulates formation of novel microvessels and invasiveness of tumor cells. In their essence, both of the vicious circles are processes allowing tumor cells to adapt to an underoxygenated tumor milieu. These processes play an important role in tumor progression, which reflects a specific type of evolution of cancer cells. Late effects of this evolution include appearance of highly aggressive, chemo- and radiotherapy resistant neoplastic cells. Increased adaptation capabilities of such cancer cells have a negative influence on the therapeutic process. Effective therapeutic strategies should not be directed against single cancer cell markers; instead, they should be targeted so as to break both vicious cycles. Herein we discuss several such strategies. In our opinion, effective therapeutic approaches must include a combination of several agents that recognize and simultaneously break both vicious cycles, i.e. vascularization and invasiveness. Also, agents that decrease hypoxia in cancer cells, for example drugs inhibiting activity of HIF-1α, might also prove therapeutically effective in such approaches.
authors.affiliation: Centrum Badań Translacyjnych i Biologii Molekularnej Nowotworów, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, ul. Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. sszala@io.gliwice.pl
authors.forename: Stanisław
authors.initials: S
authors.lastname: Szala
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jarosz
authors.forename: Ryszard
authors.initials: R
authors.lastname: Smolarczyk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cichoń
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D005909:Glioblastoma / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit