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Over forty years of bladder cancer glycobiology: Where do glycans stand facing precision oncology?

2017; Impact Journals LLC; Volume: 8; Issue: 53 Linguagem: Inglês

10.18632/oncotarget.19433

1949-2553

Rita Azevedo, Andreia Peixoto, Cristiana Gaiteiro, Elisabete Fernandes, Manuel Neves, Luís Lima, Lúcio Lara Santos, José Alexandre Ferreira,

Ubiquitin and proteasome pathways

// Rita Azevedo 1,2,* , Andreia Peixoto 1,2,3,4,* , Cristiana Gaiteiro 1 , Elisabete Fernandes 1,2,4,5 , Manuel Neves 1,2 , Luís Lima 1,4,6 , Lúcio Lara Santos 1,7 and José Alexandre Ferreira 1,2,4,6 1 Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal 2 Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal 3 New Therapies Group, INEB-Institute for Biomedical Engineering, Porto, Portugal 4 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal 5 Biomaterials for Multistage Drug and Cell Delivery, INEB-Institute for Biomedical Engineering, Porto, Portugal 6 Glycobiology in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal 7 Department of Surgical Oncology, Portuguese Institute of Oncology, Porto, Portugal * These authors have contributed equally to this work Correspondence to: José Alexandre Ferreira, email: // Keywords : cancer glycobiology, bladder cancer, glycoproteomics, glycomics, precision medicine Received : March 13, 2017 Accepted : June 19, 2017 Published : July 21, 2017 Abstract The high molecular heterogeneity of bladder tumours is responsible for significant variations in disease course, as well as elevated recurrence and progression rates, thereby hampering the introduction of more effective targeted therapeutics. The implementation of precision oncology settings supported by robust molecular models for individualization of patient management is warranted. This effort requires a comprehensive integration of large sets of panomics data that is yet to be fully achieved. Contributing to this goal, over 40 years of bladder cancer glycobiology have disclosed a plethora of cancer-specific glycans and glycoconjugates (glycoproteins, glycolipids, proteoglycans) accompanying disease progressions and dissemination. This review comprehensively addresses the main structural findings in the field and consequent biological and clinical implications. Given the cell surface and secreted nature of these molecules, we further discuss their potential for non-invasive detection and therapeutic development. Moreover, we highlight novel mass-spectrometry-based high-throughput analytical and bioinformatics tools to interrogate the glycome in the postgenomic era. Ultimately, we outline a roadmap to guide future developments in glycomics envisaging clinical implementation.