Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.

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Publisher: BioMed Central Ltd.
Document Type: Article
Length: 11,350 words
Lexile Measure: 1460L

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Abstract :

Solid tumors often grow in a micro-environment characterized by Hypoxia and chronic ER stress both induce chemoresistance. In this review we discuss the multiple and interconnected circuitries that link hypoxic environment, chronic ER stress and chemoresistance. We suggest that hypoxia and ER stress train and select the cells more adapted to survive in unfavorable conditions, by activating pleiotropic mechanisms including apoptosis inhibition, metabolic rewiring, anti-oxidant defences, drugs efflux. This adaptative process unequivocally expands clones that acquire resistance to chemotherapy. We believe that pharmacological inhibitors of HIF-1[alpha] and modulators of ER stress, although characterized by low specificty and anti-cancer efficacy when used as single agents, may be repurposed as chemosensitizers against hypoxic and chemorefractory tumors in the next future. Keywords: Hypoxia, Hypoxia-inducible factor-1[alpha], Endoplasmic reticulum stress, Unfolded protein response, Chemoresistance

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Gale Document Number: GALE|A650603023