Glycoproteogenomics: Setting the Course for Next-generation Cancer Neoantigen Discovery for Cancer Vaccines.
10.1016/j.gpb.2021.03.005
- Author:
José Alexandre FERREIRA
1
,
2
,
3
;
Marta RELVAS-SANTOS
1
,
2
,
4
;
Andreia PEIXOTO
1
,
5
;
André M N SILVA
6
;
Lúcio LARA SANTOS
1
,
2
,
7
Author Information
1. Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto 4200-072, Portugal
2. Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto 4050-313, Portugal
3. Porto Comprehensive Cancer Center (P.ccc), Porto 4200-072, Portugal. Electronic address: jose.a.ferreira@ipoporto.min-saude.pt.
4. REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, Porto 4169-007, Portugal.
5. Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto 4050-313, Portugal.
6. REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, Porto 4169-007, Portugal.
7. Porto Comprehensive Cancer Center (P.ccc), Porto 4200-072, Portugal.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
Cancer neoantigens;
Glycoproteogenomics;
Glycosylation;
Oncoproteogenomics;
Precision oncology
- From:
Genomics, Proteomics & Bioinformatics
2021;19(1):25-43
- CountryChina
- Language:English
-
Abstract:
Molecular-assisted precision oncology gained tremendous ground with high-throughput next-generation sequencing (NGS), supported by robust bioinformatics. The quest for genomics-based cancer medicine set the foundations for improved patient stratification, while unveiling a wide array of neoantigens for immunotherapy. Upfront pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target effects. However, the low mutational burden presented by many lesions challenges the generalization of these solutions, requiring the diversification of neoantigen sources. Oncoproteogenomics utilizing customized databases for protein annotation by mass spectrometry (MS) is a powerful tool toward this end. Expanding the concept toward exploring proteoforms originated from post-translational modifications (PTMs) will be decisive to improve molecular subtyping and provide potentially targetable functional nodes with increased cancer specificity. Walking through the path of systems biology, we highlight that alterations in protein glycosylation at the cell surface not only have functional impact on cancer progression and dissemination but also originate unique molecular fingerprints for targeted therapeutics. Moreover, we discuss the outstanding challenges required to accommodate glycoproteomics in oncoproteogenomics platforms. We envisage that such rationale may flag a rather neglected research field, generating novel paradigms for precision oncology and immunotherapy.
