Where Ideas grow
Cancer Drug Resistance


Some tumour cells including the cancer stem cells are multidrug resistant (MDR). Our overall objectives are to:
i) Identify and validate novel molecular targets to overcome MDR in cancer;
ii) Identify novel therapeutic approaches to target MDR tumour cells, particularly the cancer stem cells;
iii) Identify novel means to diagnose MDR and minimal residual disease in haematological tumours.



i) Regarding the identification of novel molecular targets to overcome MDR, we have been focusing on molecular mechanisms related to the MDR phenotype, particularly those related to the metabolic alterations of MDR cells and to the intercellular communication mediated by extracellular vesicles (exosomes and microvesicles) shed by MDR cells. We identified metabolic alterations in MDR cells, which may be transferred to drug-sensitive cells by extracellular vesicles (exosomes and microvesicles) 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) Regarding the study of novel therapeutic approaches to target MDR tumour cells, we have been studying novel potent small molecule inhibitors of the MDR phenotype (collaborations with CIIMAR, FFUP, UCIBIO/REQUIMTE) and nanotechnology-based strategies aiming to target particularly the cancer stem cells or tumour initiating cells (collaboration with CNC). More recently we have initiated a collaboration with the MIT (USA), aiming to study metakaryotic stem cells.

iii) Regarding the identification of means to diagnose a MDR phenotype in order to support clinical decisions, we are identifying tumour biomarkers on circulating tumour extracellular vesicles and on microRNAs obtained from liquid biopsies of patients with haematological cancers (acute myeloid leukaemia or multiple myeloma). 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
Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles. Trends in Molecular Medicine21(10):595-608, 2015. [Journal: Review] [CI: 32] [IF: 9,3]
DOI: 10.1016/j.molmed.2015.08.002 SCOPUS: 84942521471

The network of P-glycoprotein and microRNAs interactions. International Journal of Cancer135(2):253-263, 2014. [Journal: Review] [CI: 34] [IF: 5,1]
DOI: 10.1002/ijc.28500 SCOPUS: 84900001904

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: 17] [IF: 4,1]
DOI: 10.1038/srep44541 SCOPUS: 85015308172

Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine. ACS Nano10(4):3886-3899, 2016. [Journal: Review] [CI: 138] [IF: 13,9]
DOI: 10.1021/acsnano.5b08015 SCOPUS: 84968866526

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: 19] [IF: 4,7]
DOI: 10.1016/j.bbagen.2015.12.011 SCOPUS: 84953790097

Therapy-induced enrichment of putative lung cancer stem-like cells. International Journal of Cancer134(6):1270-1278, 2014. [Journal: Article] [CI: 35] [IF: 5,1]
DOI: 10.1002/ijc.28478 SCOPUS: 84891825186

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: 6] [IF: 6,5]
DOI: 10.1016/j.canlet.2017.02.024 SCOPUS: 85014640901

Understanding cancer drug resistance by developing and studying resistant cell line models. Current Cancer Drug Targets16(3):226-237, 2016. [Journal: Article] [CI: 5] [IF: 3]
SCOPUS: 84958952995

MicroRNAs in cancer drug resistance and drug sensitivity. MicroRNAs: Key Regulators of Oncogenesis9783319037257:251-293, 2014. [Book: Chapter]
DOI: 10.1007/978-3-319-03725-7_11 SCOPUS: 84930447379

Targeting miR-21 induces autophagy and chemosensitivity of leukemia cells. Current Drug Targets14(10):1135-1143, 2013. [Journal: Article] [CI: 58] [IF: 3,6]
DOI: 10.2174/13894501113149990185 SCOPUS: 84881353774