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What sustains the multidrug resistance phenotype beyond ABC efflux transporters? Looking beyond the tip of the iceberg


Alexa-Stratulat, Teodora; Pešić, Milica; Čipak Gašparović , Ana; Trougakos, Ioannis; Riganti, Chiara
What sustains the multidrug resistance phenotype beyond ABC efflux transporters? Looking beyond the tip of the iceberg // Drug resistance updates, 46 (2019), 100643, 25 doi:10.1016/j.drup.2019.100643 (međunarodna recenzija, pregledni rad, znanstveni)


Naslov
What sustains the multidrug resistance phenotype beyond ABC efflux transporters? Looking beyond the tip of the iceberg

Autori
Alexa-Stratulat, Teodora ; Pešić, Milica ; Čipak Gašparović , Ana ; Trougakos, Ioannis ; Riganti, Chiara

Izvornik
Drug resistance updates (1368-7646) 46 (2019); 100643, 25

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
ATP-binding cassette transporters ; Oxidative-reductive metabolism ; Mitochondria ; Endoplasmic reticulum ; Proteasome ; Autophagy ; Lysosomes

Sažetak
Identification of multidrug (MDR) efflux transporters that belong to the ATP-Binding Cassette (ABC) superfamily, represented an important breakthrough for understanding cancer multidrug resistance (MDR) and its possible overcoming. However, recent data indicate that drug resistant cells have a complex intracellular physiology that involves constant changes in energetic and oxidative-reductive metabolic pathways, as well as in the molecular circuitries connecting mitochondria, endoplasmic reticulum (ER) and lysosomes. The aim of this review is to discuss the key molecular mechanisms of cellular reprogramming that induce and maintain MDR, beyond the presence of MDR efflux transporters. We specifically highlight how cancer cells characterized by high metabolic plasticity – i.e. cells able to shift the energy metabolism between glycolysis and oxidative phosphorylation, to survive both the normoxic and hypoxic conditions, to modify the cytosolic and mitochondrial oxidative-reductive metabolism, are more prone to adapt to exogenous stressors such as anti-cancer drugs and acquire a MDR phenotype. Similarly, we discuss how changes in mitochondria dynamics and mitophagy rates, changes in proteome stability ensuring non-oncogenic proteostatic mechanisms, changes in ubiquitin/proteasome- and autophagy/lysosome-related pathways, promote the cellular survival under stress conditions, along with the acquisition or maintenance of MDR. After dissecting the complex intracellular crosstalk that takes place during the development of MDR, we suggest that mapping the specific adaptation pathways underlying cell survival in response to stress and targeting these pathways with potent pharmacologic agents may be a new approach to enhance therapeutic efficacy against MDR tumors.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Ustanove
Institut "Ruđer Bošković", Zagreb

Autor s matičnim brojem:
Ana Čipak Gašparović, (242341)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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