A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.

Autor: Carels N; Platform of Biological System Modeling, Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil., Sgariglia D; Engenharia de Sistemas e Computação, Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-972, RJ, Brazil., Junior MGV; Computational Modeling of Biological Systems, Scientific Computing Program (PROCC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil., Lima CR; Platform of Biological System Modeling, Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil., Carneiro FRG; Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil.; Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil.; Program of Immunology and Tumor Biology, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, RJ, Brazil., Silva GFD; Platform of Biological System Modeling, Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil., Silva FABD; Computational Modeling of Biological Systems, Scientific Computing Program (PROCC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil., Scardini R; Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, RJ, Brazil.; Program of Immunology and Tumor Biology, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, RJ, Brazil.; Centro de Ciências Biológicas e da Saúde (CCBS), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro 22290-255, RJ, Brazil., Tuszynski JA; Dipartimento di Ingegneria Meccanica e Aerospaziale (DIMEAS), Politecnico di Torino, 10129 Turin, Italy.; Department of Data Science and Engineering, The Silesian University of Technology, 44-100 Gliwice, Poland.; Department of Physics, University of Alberta, Edmonton, AB T6G 2J1, Canada., Andrade CV; Department of Pathology, Instituto Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 22250-020, RJ, Brazil., Monteiro AC; Laboratory of Osteo and Tumor Immunology, Department of Immunobiology, Fluminense Federal University, Rio de Janeiro 24210-201, RJ, Brazil., Martins MG; Chemical Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, RJ, Brazil., Silva TGD; Chemical Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, RJ, Brazil., Ferraz H; Chemical Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, RJ, Brazil., Finotelli PV; Laboratório de Nanotecnologia Biofuncional, Departamento de Produtos Naturais e Alimentos, Faculdade de Farmácia, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, RJ, Brazil., Balbino TA; Nanotechnology Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, RJ, Brazil., Pinto JC; Chemical Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, RJ, Brazil.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Nov 08; Vol. 24 (22). Date of Electronic Publication: 2023 Nov 08.
DOI: 10.3390/ijms242216098
Abstrakt: We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.
Databáze: MEDLINE
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