Drug Response and Resistance

The general aim is to study drug response at the cellular level, and its role in determining the outcome of therapy. Particular emphasis is placed on the molecular mechanisms which are associated with the ability to resist therapeutic agents, specifically microRNAs that mediate breast cancer tumorigenesis and susceptibility to breast cancer drugs. Moreover, the ability of microRNAs to revert this resistance to cancer drugs through interaction with ABC transporters and gene methylation patterns, thus acting as chemosensitizers, may help create a better prognostic marker set to predict the clinical outcome of patients and optimize pharmacotherapy.
A further interest is the role of functional variants of Na/glucose transporters (SGLT2) in the pharmacodynamics of SGLT2 inhibitors. This can have a major impact in the use of SGLT2 inhibitors as oral anti-diabetic drugs in type 2 diabetes mellitus.

É dada ênfase particular aos mecanismos moleculares que estão associados à capacidade de resistir a agentes terapêuticos, especificamente microRNAs que medeiam a desenvolvimento do cancro de mama e a suscetibilidade a fármacos usados na quimioterapia. Além disso, a capacidade dos microRNAs de reverter essa resistência aos fármacos por meio da interação com transportadores ABC e padrões de metilação do gene, agindo assim como moduladores de resistência, pode ajudar a criar um conjunto de marcadores de melhor prognóstico para prever o resultado clínico dos pacientes e otimizar a farmacoterapia.
Um outro interesse é o papel das variantes funcionais dos transportadores Na/glucose (SGLT2) na farmacodinâmica dos inibidores do SGLT2. Isso pode ter um grande impacto no uso de inibidores de SGLT2 como medicamentos antidiabéticos orais no diabetes mellitus tipo 2.

Graphical Abstract

Projects

"Comprehensive Evaluation of Circulating MicroRNA as Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis", 01-10-18, PTDC/MEC-NEU/31195/ 2017, FCT

Pluriannual funding for ToxOmics from FCT::
UIDB/00009/2020 (93121007)
UIDP/00009/2020 (93121008)

Publications

Bruno C Gomes, Mónica Honrado, Ana Armada, Miguel Viveiros, José Rueff, António S Rodrigues. ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance. Int J Mol Sci. 2020 Apr 23;21(8):2985. doi: 10.3390/ijms21082985.

Kidd, K., Vylet’al, P., Schaeffer, C., Olinger, E., Živná, M., Hodaňová, K., ... & Bleyer, A. J. (2020). Genetic and clinical predictors of age of ESKD in individuals with autosomal dominant tubulointerstitial kidney disease due to UMOD mutations. Kidney international reports, 5(9), 1472-1485.

A. Armada, B.C. Gomes, M. Viveiros, J. Rueff, A.S. Rodrigues. Regulation of ABCB1 activity by microRNA-200c and microRNA-203a in breast cancer cells: the quest for microRNAs’ involvement in cancer drug resistance. Cancer Drug Resist 2019;2:897-911. doi: 10.20517/cdr.2019.24.

B.C. Gomes, J. Rueff, A.S. Rodrigues. MicroRNAs and cancer drug resistance: over two thousand characters in search of a role. Cancer Drug Resist 2019;2:618-633. doi: 10.20517/cdr.2019.55.

Calado, J., Santos, A. R., Aires, I., Lebre, F., Nolasco, F., Rueff, J., & Ramalho, J. (2018). The Na+‐coupled glucose transporter SGLT 2 interacts with its accessory unit MAP 17 in vitro and their expressions overlap in the renal proximal tubule. FEBS letters, 592(19), 3317-3326.

C. Martins, J. Rueff, A.S. Rodrigues. (2018) Myristicin. In Handbook of Foodborne Diseases (K31813). Editor Dongyou Liu. Taylor & Francis.

Gomes, B.C., Martins, M., Lopes, P., Morujão, I., Oliveira, M., Araújo, A., Rueff, J. and Rodrigues, A.S., 2016. Prognostic value of microRNA-203a expression in breast cancer. Oncology Reports, 36(3), pp.1748-1756. doi: 10.3892/or.2016.4913.

J. Rueff, A.S. Rodrigues. Cancer drug resistance: a brief overview from a genetic viewpoint. Methods Mol Biol. 2016;1395:1-18. doi: 10.1007/978-1-4939-3347-1_1.