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 language | English |
|---|---|
| Article number | 711 |
| Journal | Frontiers in Pharmacology |
| Volume | 9 |
| Issue number | JUN |
| DOIs | |
| Publication status | Published - Jul 10 2018 |
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Keywords
- Anticancer targeted therapies
- Cancer cell proliferation
- Chaperone activity
- Endoplasmic reticulum stress
- Sigma receptors
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
Sigma receptors as endoplasmic reticulum stress "gatekeepers" and their modulators as emerging new weapons in the fight against cancer. / Tesei, Anna; Cortesi, Michela; Zamagni, Alice; Arienti, Chiara; Pignatta, Sara; Zanoni, Michele; Paolillo, Mayra; Curti, Daniela; Rui, Marta; Rossi, Daniela; Collina, Simona.
In: Frontiers in Pharmacology, Vol. 9, No. JUN, 711, 10.07.2018.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Sigma receptors as endoplasmic reticulum stress "gatekeepers" and their modulators as emerging new weapons in the fight against cancer
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
PY - 2018/7/10
Y1 - 2018/7/10
N2 - 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.
AB - 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.
KW - Anticancer targeted therapies
KW - Cancer cell proliferation
KW - Chaperone activity
KW - Endoplasmic reticulum stress
KW - Sigma receptors
UR - http://www.scopus.com/inward/record.url?scp=85049922651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049922651&partnerID=8YFLogxK
U2 - 10.3389/fphar.2018.00711
DO - 10.3389/fphar.2018.00711
M3 - Review article
AN - SCOPUS:85049922651
VL - 9
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
IS - JUN
M1 - 711
ER -