title: Targeting hypoxic response for cancer therapy.
abstract: Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis. Moreover, during the adaptation to a HTM cancer cells undergo deep changes in mitochondrial functions such as "Warburg effect" and the "reverse Warburg effect".This review aims to provide an overview of the characteristics of the HTM, with particular focus on novel therapeutic strategies currently in clinical trials, targeting the adaptive response to hypoxia of cancer cells.
authors: Genetics-Department of Biology, University of Pisa, Pisa, Italy.
authors: Elisa
authors: E
authors: Paolicchi
authors: Genetics-Department of Biology, University of Pisa, Pisa, Italy.
authors: Federica
authors: F
authors: Gemignani
authors: School of Environment and Life Sciences, College of Science and Technology, University of Salford, Salford, UK.
authors: Marija
authors: M
authors: Krstic-Demonacos
authors: Department of Integrative Oncology, BC Cancer Research Centre, BC Cancer Agency and Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Shoukat
authors: S
authors: Dedhar
authors: School of Environment and Life Sciences, College of Science and Technology, University of Salford, Salford, UK.
authors: Luciano
authors: L
authors: Mutti
authors: Genetics-Department of Biology, University of Pisa, Pisa, Italy.
authors: Stefano
authors: S
authors: Landi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents
keywords: Warburg effect; cancer stem cells; clinical trials; epithelial mesenchymal transition; hypoxia