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Pregled bibliografske jedinice broj: 1067956

Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance


Erin, Nuray; Grahovac, Jelena; Brozović, Anamaria; Effert, Thomas
Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance // Drug resistance updates (2020) doi:10.1016/j.drup.2020.100715 (pregledni, prihvaćen)


Naslov
Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance

Autori
Erin, Nuray ; Grahovac, Jelena ; Brozović, Anamaria ; Effert, Thomas

Vrsta, podvrsta
Radovi u časopisima, pregledni

Izvornik
Drug resistance updates (2020)

Status rada
Prihvaćen

Ključne riječi
Chemotherapy ; Hypoxia ; Inflammation ; Microenvironment ; Multidrug resistance ; Small molecules ; Targeted therapy

Sažetak
It is well established that multifactorial drug resistance hinders successful cancer treatment. Tumor cell interactions with the tumor microenvironment (TME) is crucial in epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR). TME-induced factors secreted by cancer cells and cancer-associated fibroblasts (CAFs) create an inflammatory microenvironment by recruiting immune cells. CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) and inflammatory tumor associated macrophages (TAMs) are main immune cell types which further enhance chronic inflammation. Chronic inflammation nurture tumor-initiating/cancer stem-like cells (CSCs) induce both EMT and MDR leading to tumor relapses. Pro-thrombotic microenvironment created by inflammatory cytokines and chemokines from TAMs, MDSCs and CAFs is also involved in EMT and MDR. MDSCs are the most common mediators of immunosuppression and are also involved in resistance to targeted therapies, e.g. BRAF inhibitors and oncolytic viruses-based therapies. Expansion of both cancer and stroma cells causes hypoxia by hypoxia-inducible transcription factors (e.g. HIF-1α) resulting in drug resistance. TME factors induce the expression of transcriptional EMT factors, MDR and metabolic adaptation of cancer cells. Promoters of several ATP-binding cassette (ABC) transporter genes contain binding sites for canonical EMT transcription factors, e.g. ZEB, TWIST and SNAIL. Changes in glycolysis, oxidative phosphorylation and autophagy during EMT also promote MDR. Conclusively, EMT signaling simultaneously increases MDR. Owing to the multifactorial nature of MDR, targeting one mechanism seems to be non-sufficient to overcome resistance. Targeting inflammatory processes by immune modulatory compounds such as mTOR inhibitors, demethylating agents, low-dosed histone deacetylase inhibitors may decrease MDR. Targeting EMT and metabolic adaptation by small molecular inhibitors might also reverse MDR. In this review, we summarize evidence for TME components as causative factors of EMT and anticancer drug resistance.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2016-06-1036 - Određivanje ključnih molekula epitelno-mezenhimalne tranzicije kao mogućih ciljeva za terapiju raka jajnika (Anamaria Brozović, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Profili:

Avatar Url Anamaria Brozović (autor)

Citiraj ovu publikaciju

Erin, Nuray; Grahovac, Jelena; Brozović, Anamaria; Effert, Thomas
Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance // Drug resistance updates (2020) doi:10.1016/j.drup.2020.100715 (pregledni, prihvaćen)
Erin, N., Grahovac, J., Brozović, A. & Effert, T. (2020) Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Prihvaćen za objavljivanje u Drug resistance updates. [Preprint] doi:10.1016/j.drup.2020.100715.
@unknown{unknown, year = {2020}, DOI = {10.1016/j.drup.2020.100715}, keywords = {Chemotherapy, Hypoxia, Inflammation, Microenvironment, Multidrug resistance, Small molecules, Targeted therapy}, journal = {Drug resistance updates}, doi = {10.1016/j.drup.2020.100715}, title = {Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance}, keyword = {Chemotherapy, Hypoxia, Inflammation, Microenvironment, Multidrug resistance, Small molecules, Targeted therapy} }

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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