Logo do repositório

Percorrer por autor "Vincente, Luana Pimenta"

A mostrar 1 - 1 de 1
  • Repurposing of CFTR modulator drugs in the context of colorectal cancer
    Publication . Vincente, Luana Pimenta; Matos, Paulo; Jordan, Peter
    Colorectal cancer (CRC) remains one of the leading causes of cancer death worldwide and is considered to arise from genetic and epigenetic changes due to interactions between the tumor and the microenvironment that surrounds it. Recently, the chloride and bicarbonate channel CFTR (cystic fibrosis transmembrane conductance regulator) was implicated in CRC etiology, since a decreased CFTR expression is associated to higher aggressiveness and lower survival in sporadic CRC. Moreover, CFTR mutations are the cause for the autosomal recessive disease cystic fibrosis (CF), and individuals with CF have a higher risk of developing CRC. Several CFTR modulator drugs have been recently clinically approved to improve CFTR functional expression in CF individuals. The current Masters’ project aimed to determine if these drugs can also be used to improve CFTR abundance in non-CF CRC cells, and whether these could be used to reduce their oncogenic properties. For this purpose, four CRC cell lines, with different CFTR expression levels, were cultured and treated with three CFTR modulator drugs, individually and in combination. It was observed that the combination treatment with the three drugs significantly increased CFTR protein levels in the Caco-2 and DLD-1 cells, but had no significant impact in either HCT116 or HT29 cells, likely due to their particular genetic and epigenetic backgrounds. Importantly, treatment with CFTR modulators significantly inhibited migration of Caco-2 and DLD-1 cells, without markedly impacting their viability. These findings suggest that CFTR modulators have potential as therapeutic agents to counteract the oncogenic properties of CRC cells with specific genetic and epigenetic profiles. However, the impact of CFTR modulator treatment in CRC development will need to be validated in vivo using mouse models. Repurposing these modulators for CRC treatment could enhance outcomes for CRC patients while also reducing costs for CF patients by expanding the clinical applications of these drugs.
    2025-03-20Dissertação de mestrado Acesso restrito Ver mais