Crosstalk between endoplasmic reticulum stress and multidrug-resistant cancers: hope or frustration

Abstract

Endoplasmic reticulum stress (ERS) is a kind of cell response for coping with hypoxia and other stresses. Pieces of evidence show that continuous stress can promote the occurrence, development, and drug resistance of tumors through the unfolded protein response. Therefore, the abnormal ac-tivation of ERS and its downstream signaling pathways not only can regulate tumor growth and metastasis but also profoundly affect the efficacy of antitumor therapy. Therefore, revealing the molecular mechanism of ERS may be expected to solve the problem of tumor multidrug resistance (MDR) and become a novel strategy for the treatment of refractory and recurrent tumors. This re-view summarized the mechanism of ERS and tumor MDR, reviewed the relationship between ERS and tumor MDR, introduced the research status of tumor tissue and ERS, and previewed the prospect of targeting ERS to improve the therapeutic effect of tumor MDR. This article aims to provide researchers and clinicians with new ideas and inspiration for basic antitumor treatment.

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas—A Narrative Review

“…In RCC, it has been documented that the response to cellular stress interferes with ROS production, angiogenesis, mitochondrial quality, tumor metabolism, inflammation, genetic instability, and the tumor microenvironment (TME) [8,10,[20][21][22]. Low levels of chronic oxidative stress act as a driving force for the malignant transformation of renal epithelial cells [15,23,24].…”

“…Cancer cells alter normal responses to oncogenic stress to redirect them towards supporting growth, even at the expense of organism integrity and homeostasis. The cellular stress response is a translational program of adaptive response activated by oncogenic stress, allowing a cell to survive in the presence of threatening factors, leading to cancer progression [8,[20][21][22].…”

Unfolded Protein Response: From cellular stress to disease pathogenesis, with insights into platelet biology

“…The adaptive response induced by the UPR helps cancer cells survive and adapt to cytotoxic treatments. For example, PERK activation can attenuate apoptosis and increase drug resistance, leading to treatment failure and disease recurrence 105,106 . 4.…”

Endoplasmic reticulum localized TMEM33 domain‐containing protein is crucial for all life cycle stages of the malaria parasite

“…Moreover, other important UPR regulators like GRP78 and eIF2α have also been investigated for antimalarial agent development (Chen et al, 2018;Zhang et al, 2017). It is known that in higher eukaryotes, UPR activation in response to ER stress may lead to the induction of apoptosis, autophagy, or resistance to chemotherapeutic drugs (Kim et al, 2008;Kroemer et al, 2010;Ogata et al, 2006;Qing et al, 2023), and to some extent in parasitic protozoa as well (Dolai & Adak, 2014;Goldshmidt et al, 2010;Lee et al, 2007;Tsiatsiani et al, 2011). Therefore, identification of new molecular players which regulate the ER functioning may help in the development of novel antimalarial therapy.…”