Associação Portuguesa de Investigação em Cancro
The multi-factorial nature of clinical multidrug resistance in cancer
The multi-factorial nature of clinical multidrug resistance in cancer
Several experts from COST Action STRATAGEM - “New diagnostic and therapeutic tools against multidrug resistant tumors”, joined efforts to write an up-to-date, focused and thought-provoking review on the multi-disciplinary and interdisciplinary features of multidrug resistant cancers. It is necessary to identify and understand the various molecular mechanisms behind clinical multidrug resistance, in order to develop new targeted therapeutic strategies to overcome cancer therapeutic failure. The diverse factors involved in multidrug resistance highlight the relevance of novel precision medicine and real-time personalized treatment modalities, taking into consideration individual cancer patients.
Authors and Affiliations:
Yehuda G. Assaraf - The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa, 3200000, Israel
Anamaria Brozovic - Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia
Ana Cristina Gonçalves - Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, FMUC, Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR) - Group of Environment Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; CNC. IBILI, University of Coimbra, Portugal
Dana Jurkovicova - Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
Aija Linē - Latvian Biomedical Research and Study Centre, Riga, Latvia
Miguel Machuqueiro - BioISI-Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, C8 Building, Campo Grande, 1749-016, Lisboa, Portugal; Departamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
Simona Saponara - Department of Life Sciences, University of Siena, Siena, Italy
Ana Bela Sarmento-Ribeiro - Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, FMUC, Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR) - Group of Environment Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; CNC. IBILI, University of Coimbra, Portugal; Clinical Hematology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal
Cristina P.R. Xavier - i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
M. Helena Vasconcelos - i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; Department of Biological Sciences, FFUP - Faculty of Pharmacy of the University of Porto, Porto, Portugal
Abstract:
Curative cancer therapy remains a major challenge particularly in cancers displaying multidrug resistance (MDR). The MDR phenotype is characterized by cross-resistance to a wide array of anticancer drugs harboring distinct structures and mechanisms of action. The multiple factors involved in mediating MDR may include host factors, tumor factors as well as tumor-host interactions. Among the host factors are genetic variants and drug-drug interactions. The plethora of tumor factors involves decreased drug uptake primarily via impaired influx transporters, increased drug efflux predominantly due to the overexpression of MDR efflux transporters of the ATP-binding cassette superfamily or due to drug efflux mediated by extracellular vesicles (EVs) or drug-loaded lysosomes undergoing exocytosis, deregulation of cell death mechanisms (i.e. anti-apoptotic modalities), enhanced DNA damage repair, epigenetic alterations and/or deregulation of microRNAs. The intratumor heterogeneity and dynamics, along with cancer stem cell plasticity, are important tumor factors. Among the tumor-host interactions are the role of the tumor microenvironment, selective pressure of various stressor conditions and agents, acidic pH and the intracellular transfer of traits mediated by EVs. The involvement of these diverse factors in MDR, highlights the need for precision medicine and real-time personalized treatments of individual cancer patients. In this review, written by a group of researchers from COST Action STRATAGEM “New diagnostic and therapeutic tools against multidrug resistant tumors”, we aim to bring together these multi-disciplinary and interdisciplinary features of MDR cancers. Importantly, it is becoming increasingly clear that deciphering the molecular mechanisms underlying anticancer drug resistance, will pave the way towards the development of novel precision medicine treatment modalities that are able to surmount distinct and well-defined mechanisms of anticancer drug resistance.
Journal: Drug Resistance Updates
Link: https://www.ncbi.nlm.nih.gov/pubmed/31585396