title: Switching off malignant mesothelioma: exploiting the hypoxic microenvironment.
abstract: Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention.
authors.affiliation: Laboratory for Advanced Genome Analysis, Vancouver Prostate Centre, BC, Canada; Department of Urologic Sciences, University of British Columbia, BC, Canada; Department of Experimental Therapeutics, BC Cancer Agency, BC, Canada.
authors.forename: Noushin
authors.initials: N
authors.lastname: Nabavi
authors.affiliation: Department of Integrative Oncology, BC Cancer Agency, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Bennewith
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Churg
authors.affiliation: Department of Urologic Sciences, University of British Columbia, BC, Canada; Department of Experimental Therapeutics, BC Cancer Agency, BC, Canada.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory for Advanced Genome Analysis, Vancouver Prostate Centre, BC, Canada; Department of Urologic Sciences, University of British Columbia, BC, Canada.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.affiliation: Italian Group for Research and Therapy for Mesothelioma (GIMe) & School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom.
authors.forename: Luciano
authors.initials: L
authors.lastname: Mutti
keywords: DNA damage; angiogenesis; cell cycle; hypoxia; mesothelioma; metabolism; proteolysis; solid tumors