Targeting the Unfolded Protein Response in Hormone-Regulated Cancers

Yang Jin; Fahri Saatcioglu

doi:10.1016/j.trecan.2019.12.001

Targeting the Unfolded Protein Response in Hormone-Regulated Cancers

Trends Cancer. 2020 Feb;6(2):160-171. doi: 10.1016/j.trecan.2019.12.001. Epub 2020 Jan 16.

Authors

Yang Jin¹, Fahri Saatcioglu²

Affiliations

¹ Department of Biosciences, University of Oslo, Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway. Electronic address: yang.jin@ibv.uio.no.
² Department of Biosciences, University of Oslo, Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway. Electronic address: fahris@ibv.uio.no.

PMID: 32061305
DOI: 10.1016/j.trecan.2019.12.001

Abstract

Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One of these is the unfolded protein response (UPR), a highly conserved signaling pathway that is mounted in response to endoplasmic reticulum (ER) stress. Recent work showed that steroid hormones, in particular estrogens and androgens, regulate the canonical UPR pathways in breast cancer (BCa) and prostate cancer (PCa). In addition, UPR has pleiotropic effects in advanced disease and development of therapy resistance. These findings implicate the UPR pathway as a novel target in hormonally regulated cancers in the clinic. Here, we review the potential therapeutic value of recently developed small molecule inhibitors of UPR in hormone regulated cancers.

Keywords: androgens; breast cancer; estrogens; prostate cancer; therapeutic targets; unfolded protein response.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Activating Transcription Factor 4 / genetics
Activating Transcription Factor 4 / metabolism
Activating Transcription Factor 6 / metabolism
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Breast Neoplasms / drug therapy*
Breast Neoplasms / genetics
Breast Neoplasms / pathology
Drug Resistance, Neoplasm / genetics
Endoplasmic Reticulum Stress / drug effects
Endoplasmic Reticulum Stress / genetics
Endoribonucleases / antagonists & inhibitors
Endoribonucleases / metabolism
Eukaryotic Initiation Factor-2 / metabolism
Female
Gene Expression Regulation, Neoplastic / drug effects
Gonadal Steroid Hormones / antagonists & inhibitors
Gonadal Steroid Hormones / metabolism*
Humans
Male
Phosphorylation / drug effects
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / genetics
Prostatic Neoplasms / pathology
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / metabolism
Proteostasis / drug effects
Signal Transduction / drug effects
Signal Transduction / genetics
Unfolded Protein Response / drug effects*
Unfolded Protein Response / genetics
X-Box Binding Protein 1 / genetics
eIF-2 Kinase / antagonists & inhibitors
eIF-2 Kinase / metabolism

Substances

Activating Transcription Factor 6
Antineoplastic Agents
Eukaryotic Initiation Factor-2
Gonadal Steroid Hormones
X-Box Binding Protein 1
Activating Transcription Factor 4
ERN1 protein, human
PERK kinase
Protein Serine-Threonine Kinases
eIF-2 Kinase
Endoribonucleases