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

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: 46] [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: 300] [IF: 13,9]
DOI: 10.1021/acsnano.5b08015 SCOPUS: 84968866526

Gonçalves A.C., Richiardone E., Jorge J., Polónia B., Xavier C.P.R., Salaroglio I.C., Riganti C., Vasconcelos M.H., Corbet C., Sarmento-Ribeiro A.B.,
Impact of cancer metabolism on therapy resistance – Clinical implications. Drug Resistance Updates59:, 2021. [Journal: Review] [CI: 6] [IF: 22,8]
DOI: 10.1016/j.drup.2021.100797 SCOPUS: 85121838523

Peixoto da Silva S., Caires H.R., Bergantim R., Guimarães J.E., Vasconcelos M.H.,
miRNAs mediated drug resistance in hematological malignancies. Seminars in Cancer Biology83:283-302, 2022. [Journal: Review] [CI: 4] [IF: 17,0 (*)]
DOI: 10.1016/j.semcancer.2021.03.014 SCOPUS: 85104141539

Xavier C.P.R., Castro I., Caires H.R., Ferreira D., Cavadas B., Pereira L., Santos L.L., Oliveira M.J., Vasconcelos M.H.,
Chitinase 3-like-1 and fibronectin in the cargo of extracellular vesicles shed by human macrophages influence pancreatic cancer cellular response to gemcitabine. Cancer Letters501:210-223, 2021. [Journal: Article] [CI: 20] [IF: 9,8]
DOI: 10.1016/j.canlet.2020.11.013 SCOPUS: 85096944364

Sousa D., Matthiesen R., Lima R.T., Helena Vasconcelos M.,
Deep sequencing analysis reveals distinctive non-coding RNAs when comparing tumor multidrug-resistant cells and extracellular vesicles with drug-sensitive counterparts. Cancers12(1):, 2020. [Journal: Article] [CI: 7] [IF: 6,6]
DOI: 10.3390/cancers12010200 SCOPUS: 85079196794

Sousa D., Lima R.T., Lopes-Rodrigues V., Gonzalez E., Royo F., Xavier C.P.R., Falcón-Pérez J.M., Vasconcelos M.H.,
Different ability of multidrug-resistant and-sensitive counterpart cells to release and capture extracellular vesicles. Cells10(11):, 2021. [Journal: Article] [CI: 1] [IF: 7,7]
DOI: 10.3390/cells10112886 SCOPUS: 85117907370

Pagano L., Salmanton-García J., Marchesi F., Busca A., Corradini P., Hoenigl M., Klimko N., Koehler P., Pagliuca A., Passamonti F., Verga L., Víšek B., Ilhan O., Nadali G., Weinbergerová B., Córdoba-Mascuñano R., Marchetti M., Collins G.P., Farina F., Cattaneo C., Cabirta A., Gomes-Silva M., Itri F., van Doesum J., Ledoux M.P., Cernan M., Jakšic O., Duarte R.F., Magliano G., Omrani A.S., Fracchiolla N.S., Kulasekararaj A., Valkovic T., Poulsen C.B., Machado M., Glenthøj A., Stoma I., Rácil Z., Piukovics K., Navrátil M., Emarah Z., Sili U., Maertens J., Blennow O., Bergantim R., García-Vidal C., Prezioso L., Guidetti A., del Principe M.I., Popova M., de Jonge N., Ormazabal-Vélez I., Fernández N., Falces-Romero I., Cuccaro A., Meers S., Buquicchio C., Antic D., Al-Khabori M., García-Sanz R., Biernat M.M., Tisi M.C., Sal E., Rahimli L., Colovic N., Schönlein M., Calbacho M., Tascini C., Miranda-Castillo C., Khanna N., Méndez G.A., Petzer V., Novák J., Besson C., Duléry R., Lamure S., Nucci M., Zambrotta G., Žák P., Seval G.C., Bonuomo V., Mayer J., López-García A., Sacchi M.V., Booth S., Ciceri F., Oberti M., Salvini M., Izuzquiza M., Nunes-Rodrigues R., Ammatuna E., Obr A., Herbrecht R., Núñez-Martín-Buitrago L., Mancini V., Shwaylia H., Sciumè M., Essame J., Nygaard M., Batinic J.,
COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). Journal of Hematology and Oncology14(1):, 2021. [Journal: Article] [CI: 39] [IF: 23,2]
DOI: 10.1186/s13045-021-01177-0 SCOPUS: 85117512005

Assaraf Y.G., Brozovic A., Gonçalves A.C., Jurkovicova D., Line A., Machuqueiro M., Saponara S., Sarmento-Ribeiro A.B., Xavier C.P.R., Vasconcelos M.H.,
The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resistance Updates46:, 2019. [Journal: Article] [CI: 167] [IF: 11]
DOI: 10.1016/j.drup.2019.100645 SCOPUS: 85072866477

Vasconcelos M.H., Caires H.R., Abols A., Xavier C.P.R., Line A.,
Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance. Drug Resistance Updates47:, 2019. [Journal: Article] [CI: 64] [IF: 11]
DOI: 10.1016/j.drup.2019.100647 SCOPUS: 85074466138

Xavier C.P.R., Belisario D.C., Rebelo R., Assaraf Y.G., Giovannetti E., Kopecka J., Vasconcelos M.H.,
The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells. Drug Resistance Updates62:, 2022. [Journal: Review] [CI: 2] [IF: 22,8 (*)]
DOI: 10.1016/j.drup.2022.100833 SCOPUS: 85128197831

Barbosa M.A.G., Xavier C.P.R., Pereira R.F., Petrikaite V., Vasconcelos M.H.,
3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs. Cancers14(1):, 2022. [Journal: Review] [CI: 4] [IF: 6,6 (*)]
DOI: 10.3390/cancers14010190 SCOPUS: 85122071208

Xavier C.P.R., Caires H.R., Barbosa M.A.G., Bergantim R., Guimarães J.E., Vasconcelos M.H.,
The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance. Cells9(5):, 2020. [Journal: Review] [CI: 56] [IF: 6,6]
DOI: 10.3390/cells9051141 SCOPUS: 85084721560