Where Ideas grow

Cancer Drug Resistance

ABOUT

Some tumour cells, including the cancer stem cells, are multidrug resistant (MDR). Our translational and clinical research aims to:

  1. Identify and validate novel molecular targets to overcome MDR in cancer;
  2. Test novel therapeutic tools to target MDR tumour cells, particularly the cancer stem cells;
  3. Identify novel means to diagnose MDR and minimal residual disease in haematological tumours.

RESEARCH

The group’s main achievements include:

I) Understanding molecular mechanisms related to the MDR phenotype, particularly those related to metabolic alterations of MDR cells and to intercellular communications mediated by extracellular vesicles shed by MDR cells or shed by macrophages. Mainly, we identified metabolic alterations in MDR cells, which may be transferred to drug-sensitive cells by extracellular vesicles released by the MDR cells (Scientific Reports, 2017). This work was possible due to collaborations with the NICB (Dublin City University, Ireland), with CIC bioGUNE (Spain) and with the University of Belgrade (Serbia).
II) Identifying novel therapeutic tools to inhibit the MDR phenotype (collaborations with CIIMAR, FFUP, UCIBIO/REQUIMTE) and to target particularly the cancer stem cells (collaboration with CNC). More recently we have initiated a collaboration with the MIT (USA), aiming to study cancer stem cells.
III) Identifying biomarkers of MDR and of minimal residual disease on circulating tumour extracellular vesicles obtained from liquid biopsies of patients with cancer, particularly haematological tumours, in order to support clinical decisions. This work is possible due to a strong collaboration with Centro Hospitalar São João (CHSJ).

The intercellular transfer of Pgp from drug resistant to drug sensitive cells may be mediated by extracellular vesicles. This confocal microscopy image shows expression of Pgp in non-Pgp expressing drug sensitive cells following co-culture with extracellular vesicles from drug resistant (Pgp-overex

Selected Publications

Sousa D., Lima R.T., Vasconcelos M.H.,
Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles. Trends in Molecular Medicine21(10):595-608, 2015. [Journal: Review] [CI: 52] [IF: 9,3]
DOI: 10.1016/j.molmed.2015.08.002 SCOPUS: 84942521471. .

Lopes-Rodrigues V., Seca H., Sousa D., Sousa E., Lima R.T., Vasconcelos M.H.,
The network of P-glycoprotein and microRNAs interactions. International Journal of Cancer135(2):253-263, 2014. [Journal: Review] [CI: 39] [IF: 5,1]
DOI: 10.1002/ijc.28500 SCOPUS: 84900001904. .

Lopes-Rodrigues V., Di Luca A., Mleczko J., Meleady P., Henry M., Pesic M., Cabrera D., Van Liempd S., Lima R.T., O'Connor R., Falcon-Perez J.M., Vasconcelos M.H.,
Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles. Scientific Reports7:, 2017. [Journal: Article] [CI: 22] [IF: 4,1]
DOI: 10.1038/srep44541 SCOPUS: 85015308172. .

Fais S., O'Driscoll L., Borras F.E., Buzas E., Camussi G., Cappello F., Carvalho J., Cordeiro Da Silva A., Del Portillo H., El Andaloussi S., Ficko Trcek T., Furlan R., Hendrix A., Gursel I., Kralj-Iglic V., Kaeffer B., Kosanovic M., Lekka M.E., Lipps G., Logozzi M., Marcilla A., Sammar M., Llorente A., Nazarenko I., Oliveira C., Pocsfalvi G., Rajendran L., Raposo G., Rohde E., Siljander P., Van Niel G., Vasconcelos M.H., Yáñez-Mó M., Yliperttula M.L., Zarovni N., Zavec A.B., Giebel B.,
Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine. ACS Nano10(4):3886-3899, 2016. [Journal: Review] [CI: 188] [IF: 13,9]
DOI: 10.1021/acsnano.5b08015 SCOPUS: 84968866526. .

Lopes-Rodrigues V., Di Luca A., Sousa D., Seca H., Meleady P., Henry M., Lima R.T., O'Connor R., Vasconcelos M.H.,
Multidrug resistant tumour cells shed more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart cells. Biochimica et Biophysica Acta - General Subjects1860(3):618-627, 2016. [Journal: Article] [CI: 25] [IF: 4,7]
DOI: 10.1016/j.bbagen.2015.12.011 SCOPUS: 84953790097. .

Freitas D.P., Teixeira C.A., Santos-Silva F., Vasconcelos M.H., Almeida G.M.,
Therapy-induced enrichment of putative lung cancer stem-like cells. International Journal of Cancer134(6):1270-1278, 2014. [Journal: Article] [CI: 41] [IF: 5,1]
DOI: 10.1002/ijc.28478 SCOPUS: 84891825186. .

Silva P.M.A., Ribeiro N., Lima R.T., Andrade C., Diogo V., Teixeira J., Florindo C., Tavares Á., Vasconcelos M.H., Bousbaa H.,
Suppression of spindly delays mitoti