The multi-factorial nature of clinical multidrug resistance in cancer

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2019

Autores

Assaraf, YG (Autor) Outra; Brozovic, A (Autor) Outra; Goncalves, AC (Autor) Outra; Jurkovicova, D (Autor) Outra; Line, A (Autor) Outra; Machuqueiro, M (Autor) Outra; Saponara, S (Autor) Outra; Sarmento Ribeiro, AB (Autor) Outra; Xavier, CPR (Autor) Outra; Helena Vasconcelos, MH (Autor) FFUP

Revista

Título: Drug Resistance Updates

Vol. 46

ISSN: 1368-7646

Editora: Elsevier

Indexação

ISI Web of Knowledge - 109 Citações

Scopus - 127 Citações

Outras Informações

ID Authenticus: P-00R-4EZ

DOI: 10.1016/j.drup.2019.100645

Abstract (EN): 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 (Le. 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 multidisciplinary 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 30