Sigma receptors as endoplasmic reticulum stress "gatekeepers" and their modulators as emerging new weapons in the fight against cancer

Anna Tesei, Michela Cortesi, Alice Zamagni, Chiara Arienti, Sara Pignatta, Michele Zanoni, Mayra Paolillo, Daniela Curti, Marta Rui, Daniela Rossi, Simona Collina

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Despite the interest aroused by sigma receptors (SRs) in the area of oncology, their role in tumor biology remains enigmatic. The predominant subcellular localization and main site of activity of SRs are the endoplasmic reticulum (ER). Current literature data, including recent findings on the sigma 2 receptor subtype (S2R) identity, suggest that SRs may play a role as ER stress gatekeepers. Although SR endogenous ligands are still unknown, a wide series of structurally unrelated compounds able to bind SRs have been identified. Currently, the identification of novel antiproliferative molecules acting via SR interaction is a challenging task for both academia and industry, as shown by the fact that novel anticancer drugs targeting SRs are in the preclinical-stage pipeline of pharmaceutical companies (i.e., Anavex Corp. and Accuronix). So far, no clinically available anticancer drugs targeting SRs are still available. The present review focuses literature advancements and provides a state-of-the-art overview of SRs, with emphasis on their involvement in cancer biology and on the role of SR modulators as anticancer agents. Findings from preclinical studies on novel anticancer drugs targeting SRs are presented in brief.

Original languageEnglish
Article number711
JournalFrontiers in Pharmacology
Volume9
Issue numberJUN
DOIs
Publication statusPublished - Jul 10 2018

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sigma Receptors
Endoplasmic Reticulum Stress
Weapons
Neoplasms
Drug Delivery Systems
Endoplasmic Reticulum
Antineoplastic Agents
Industry

Keywords

  • Anticancer targeted therapies
  • Cancer cell proliferation
  • Chaperone activity
  • Endoplasmic reticulum stress
  • Sigma receptors

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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abstract = "Despite the interest aroused by sigma receptors (SRs) in the area of oncology, their role in tumor biology remains enigmatic. The predominant subcellular localization and main site of activity of SRs are the endoplasmic reticulum (ER). Current literature data, including recent findings on the sigma 2 receptor subtype (S2R) identity, suggest that SRs may play a role as ER stress gatekeepers. Although SR endogenous ligands are still unknown, a wide series of structurally unrelated compounds able to bind SRs have been identified. Currently, the identification of novel antiproliferative molecules acting via SR interaction is a challenging task for both academia and industry, as shown by the fact that novel anticancer drugs targeting SRs are in the preclinical-stage pipeline of pharmaceutical companies (i.e., Anavex Corp. and Accuronix). So far, no clinically available anticancer drugs targeting SRs are still available. The present review focuses literature advancements and provides a state-of-the-art overview of SRs, with emphasis on their involvement in cancer biology and on the role of SR modulators as anticancer agents. Findings from preclinical studies on novel anticancer drugs targeting SRs are presented in brief.",
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AU - Tesei, Anna

AU - Cortesi, Michela

AU - Zamagni, Alice

AU - Arienti, Chiara

AU - Pignatta, Sara

AU - Zanoni, Michele

AU - Paolillo, Mayra

AU - Curti, Daniela

AU - Rui, Marta

AU - Rossi, Daniela

AU - Collina, Simona

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