Oncotarget

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

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

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Oncotarget. 2017; 8:91734-91764. https://doi.org/10.18632/oncotarget.19433

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Abstract

Rita Azevedo1,2,*, Andreia Peixoto1,2,3,4,*, Cristiana Gaiteiro1, Elisabete Fernandes1,2,4,5, Manuel Neves1,2, Luís Lima1,4,6, Lúcio Lara Santos1,7 and José Alexandre Ferreira1,2,4,6

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.


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