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