Modelagem matemática da resistência à quimioterapia: aquisição de resistência via transferência da glicoproteína-P

• Autor(a) principal: Mendonça, Thaís Madruga de Oliveira
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações do LNCC
• Texto Completo: https://tede.lncc.br/handle/tede/381
• topic: Quimioterapia; Resistência à medicamentos; Modelagem matemática; Equações diferenciais ordinárias; Câncer - Modelos matemáticos; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA

Drug resistance in cancer treatment is an obstacle to therapeutic success. Cancer cells exposed to a drug can acquire resistance to multiple drugs due to the overexpression of glycoprotein-P (P-gp) on the cell surface. The mechanism of resistance acquisition via P-gp transfer can occur through cell-cell contact or through microvesicles, which are spherical lipid bilayered structures naturally shed by cells. Considering that mathematical modeling can aid in understanding the mechanisms of resistance acquisition, this study evaluated some models proposed in the literature and developed new models to represent the in vitro dynamics of a mixture of sensitive and resistant non-small lung cancer cells. The parameters of all models were estimated via hierarchical Bayesian inference, first analyzing possible growth models for the independent growth of each cell type. The different growth models of these cell populations and subsequently the mixture models were compared using Bayesian information criteria. This analysis identified the importance of explicitly modeling microvesicles in modulating the process of resistance acquisition in in vitro mixtures of sensitive and multi-drug-resistant cells.