ER stress and/or ER-phagy in drug resistance? Three coincidences are proof

Abstract Cancer is influenced by the tumor microenvironment (TME), which includes factors such as pH, hypoxia, immune cells, and blood vessels. These factors affect cancer cell growth and behavior. The tumor microenvironment triggers adaptive responses such as endoplasmic reticulum (ER) stress, unfo...

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Main Authors: Sameer Kumar Panda, Ibone Rubio Sanchez-Pajares, Ayesha Rehman, Vitale Del Vecchio, Luigi Mele, Sandhya Chipurupalli, Nirmal Robinson, Vincenzo Desiderio
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Cell Communication and Signaling
Subjects:
Online Access:https://doi.org/10.1186/s12964-025-02232-w
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author Sameer Kumar Panda
Ibone Rubio Sanchez-Pajares
Ayesha Rehman
Vitale Del Vecchio
Luigi Mele
Sandhya Chipurupalli
Nirmal Robinson
Vincenzo Desiderio
author_facet Sameer Kumar Panda
Ibone Rubio Sanchez-Pajares
Ayesha Rehman
Vitale Del Vecchio
Luigi Mele
Sandhya Chipurupalli
Nirmal Robinson
Vincenzo Desiderio
author_sort Sameer Kumar Panda
collection DOAJ
description Abstract Cancer is influenced by the tumor microenvironment (TME), which includes factors such as pH, hypoxia, immune cells, and blood vessels. These factors affect cancer cell growth and behavior. The tumor microenvironment triggers adaptive responses such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy, posing a challenge to cancer treatment. The UPR aims to restore ER homeostasis by involving key regulators inositol-requiring enzyme-1(IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Additionally, ER-phagy, a selective form of autophagy, eliminates ER components under stress conditions. Understanding the interplay between hypoxia, ER stress, UPR, and autophagy in the tumor microenvironment is crucial for developing effective cancer therapies to overcome drug resistance. Targeting the components of the UPR and modulating ER-phagy could potentially improve the efficacy of existing cancer therapies. Future research should define the conditions under which ER stress responses and ER-phagy act as pro-survival versus pro-death mechanisms and develop precise methods to quantify ER-phagic flux in tumor cells.
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institution Kabale University
issn 1478-811X
language English
publishDate 2025-05-01
publisher BMC
record_format Article
series Cell Communication and Signaling
spelling doaj-art-ef2fa2d71a7540be8bc22be3d398a85f2025-08-20T03:53:58ZengBMCCell Communication and Signaling1478-811X2025-05-0123111410.1186/s12964-025-02232-wER stress and/or ER-phagy in drug resistance? Three coincidences are proofSameer Kumar Panda0Ibone Rubio Sanchez-Pajares1Ayesha Rehman2Vitale Del Vecchio3Luigi Mele4Sandhya Chipurupalli5Nirmal Robinson6Vincenzo Desiderio7Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”University of BasilicataCenter for Cancer Biology, University of South Australia and SA PathologyCenter for Cancer Biology, University of South Australia and SA PathologyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”Abstract Cancer is influenced by the tumor microenvironment (TME), which includes factors such as pH, hypoxia, immune cells, and blood vessels. These factors affect cancer cell growth and behavior. The tumor microenvironment triggers adaptive responses such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy, posing a challenge to cancer treatment. The UPR aims to restore ER homeostasis by involving key regulators inositol-requiring enzyme-1(IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Additionally, ER-phagy, a selective form of autophagy, eliminates ER components under stress conditions. Understanding the interplay between hypoxia, ER stress, UPR, and autophagy in the tumor microenvironment is crucial for developing effective cancer therapies to overcome drug resistance. Targeting the components of the UPR and modulating ER-phagy could potentially improve the efficacy of existing cancer therapies. Future research should define the conditions under which ER stress responses and ER-phagy act as pro-survival versus pro-death mechanisms and develop precise methods to quantify ER-phagic flux in tumor cells.https://doi.org/10.1186/s12964-025-02232-wER StressUPRER-phagyAutophagyDrug resistance
spellingShingle Sameer Kumar Panda
Ibone Rubio Sanchez-Pajares
Ayesha Rehman
Vitale Del Vecchio
Luigi Mele
Sandhya Chipurupalli
Nirmal Robinson
Vincenzo Desiderio
ER stress and/or ER-phagy in drug resistance? Three coincidences are proof
Cell Communication and Signaling
ER Stress
UPR
ER-phagy
Autophagy
Drug resistance
title ER stress and/or ER-phagy in drug resistance? Three coincidences are proof
title_full ER stress and/or ER-phagy in drug resistance? Three coincidences are proof
title_fullStr ER stress and/or ER-phagy in drug resistance? Three coincidences are proof
title_full_unstemmed ER stress and/or ER-phagy in drug resistance? Three coincidences are proof
title_short ER stress and/or ER-phagy in drug resistance? Three coincidences are proof
title_sort er stress and or er phagy in drug resistance three coincidences are proof
topic ER Stress
UPR
ER-phagy
Autophagy
Drug resistance
url https://doi.org/10.1186/s12964-025-02232-w
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