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

Team

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: 81] [IF: 9,3]
DOI: 10.1016/j.molmed.2015.08.002 SCOPUS: 84942521471. Trends in Molecular Medicine. 2015

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: 46] [IF: 5,1]
DOI: 10.1002/ijc.28500 SCOPUS: 84900001904. International Journal of Cancer. 2014

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: 38] [IF: 4,1]
DOI: 10.1038/srep44541 SCOPUS: 85015308172. Scientific Reports. 2017

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: 264] [IF: 13,9]
DOI: 10.1021/acsnano.5b08015 SCOPUS: 84968866526. ACS Nano. 2016

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: 32] [IF: 4,7]
DOI: 10.1016/j.bbagen.2015.12.011 SCOPUS: 84953790097. Biochimica et Biophysica Acta - General Subjects. 2016

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: 46] [IF: 5,1]
DOI: 10.1002/ijc.28478 SCOPUS: 84891825186. International Journal of Cancer. 2014

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 mitotic exit and exacerbates cell death response of cancer cells treated with low doses of paclitaxel. Cancer Letters394:33-42, 2017. [Journal: Article] [CI: 10] [IF: 6,5]
DOI: 10.1016/j.canlet.2017.02.024 SCOPUS: 85014640901. Cancer Letters. 2017

Xavier C.P.R., Pesic M., Helena Vasconcelos M.,
Understanding cancer drug resistance by developing and studying resistant cell line models. Current Cancer Drug Targets16(3):226-237, 2016. [Journal: Article] [CI: 14] [IF: 3]
DOI: 10.2174/1568009616666151113120705 SCOPUS: 84958952995. Current Cancer Drug Targets. 2016

Seca H., Lima R.T., Vasconcelos M.H.,
MicroRNAs in cancer drug resistance and drug sensitivity. MicroRNAs: Key Regulators of Oncogenesis9783319037257:251-293, 2014. [Book: Book Chapter] [CI: 2]
DOI: 10.1007/978-3-319-03725-7_11 SCOPUS: 84930447379. MicroRNAs: Key Regulators of Oncogenesis. 2014

Seca H., Lima R.T., Lopes-Rodrigues V., Guimarães J.E., Almeida G.M., Vasconcelos M.H.,
Targeting miR-21 induces autophagy and chemosensitivity of leukemia cells. Current Drug Targets14(10):1135-1143, 2013. [Journal: Article] [CI: 78] [IF: 3,6]
DOI: 10.2174/13894501113149990185 SCOPUS: 84881353774. Current Drug Targets. 2013

Ongoing Projects

CTEVs .: Vesículas Extracelulares tumorais circulantes para deteção minimamente invasiva de doença residual mínima em doentes com leucemia mielóide aguda
Reference: POCI-01-0145-FEDER-030457
Proponent: Ipatimup
Sponsor: FCT
From 01-JUL-18 to 30-JUN-22
Biomarkers for minimal residual disease
Reference: LOOKER
Proponent: Ipatimup
Sponsor: Celgene
From 01-MAR-19 to 31-DEC-21