Switching off malignant mesothelioma: exploiting the hypoxic microenvironment
Noushin Nabavi1,2,3, Kevin L. Bennewith4,5, Andrew Churg5, Yuzhuo Wang2,3, Colin C. Collins1,2, and Luciano Mutti6
1 Laboratory for Advanced Genome Analysis, Vancouver Prostate Centre, BC, Canada
2 Department of Urologic Sciences, University of British Columbia, BC, Canada
3 Department of Experimental Therapeutics, BC Cancer Agency, BC, Canada
4 Department of Integrative Oncology, BC Cancer Agency, BC, Canada
5 Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada
6 Italian Group for Research and Therapy for Mesothelioma (GIMe) & School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom
Correspondence:
Luciano Mutti, email:
Correspondence:
Colin C. Collins, email:
Keywords: mesothelioma, hypoxia, metabolism, cell cycle, proteolysis, DNA damage, angiogenesis, solid tumors
Received: November 22, 2016 Accepted: December 31, 2016 Published: January 01, 2017
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.
