Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials
Abstract
:1. Introduction
2. AR Expression, Genetic Polymorphisms, Function, and Regulation in Human OVCA
2.1. General Description, Classification, and Pathological Features of OVCA
2.2. Biochemical Functions of Androgen/AR Signaling (Classical vs. Non-Classical Androgen/AR Signaling)
2.3. Associations of Androgen Levels, Gene Polymorphisms, and AR Expressions with OVCA Risks
3. Androgen/AR Signaling in OVCA Experimental Models
3.1. Androgen/AR Signaling Function in the Gynecological System
3.2. Androgen/AR Signaling in OVCA Stemness
4. Current Clinical Trials of Targeting Androgen/AR Therapy in OVCA
4.1. Androgen Ablation Therapy in OVCA
4.2. AR Degradation Therapy for OVCA
4.3. Potential for the Use of Anti-Androgen/AR and Anti-PARP Combination Therapy for OVCA
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | No. of Patients | Clinical Trial | Treatment | Key Findings |
---|---|---|---|---|
Thompson et al. (1991) | 62 | NR | cyproterone acetate | 6.8% patients partially responded. |
Tumolo et al. (1994) | 32/68 | phase II | oral flutamide treatment (750 mg/day) | Combined chemotherapy was invalid with side effects. |
Van der Vange et al. (1995) | 33 | Phase II | flutamide (500 mg i.m) | 1 patients showed stable disease for 8 months. |
Vassilomanolakis et al. (1997) | 43 | phase II | flutamide (300 mg/day) | Partial response (4.3%) and disease stabilization (8.7%) in 23 patients. |
Levine et al. (2007) | 35 | phase II | bicalutamide (50 mg/daily) and goserelin (3.6 mg/mon) | Failed to prolong PFS in EOC patients |
Rachel et al. (2017) | 59 | phase II | Enzalutamide (160mg by mouth QD) | Currently recruiting patients (NCT01974765) |
Susana et al. (2020) | 42 | Phase II | abiraterone (1000mg daily) | Closured. |
Study | Cell Lines | Treatment | MOA | Key Findings |
---|---|---|---|---|
Park et al. (2016) | OVCAR-3 | Enzalutamide | NR | Showed efficacy in the ovarian cancer with AR expression. |
Lin et al. (2018) | A2780 and SKOV3 | ASC-J9 | Suppressing AR→Nanog axis | AR promotes Nanog expression which contribute to CSPCs stemness in EOC cells |
Chung et al. (2019) | HeyA8, SKOV3ip1, OVCAR-3 | Paclitaxel/ASC-J9 | Suppressing AR→ABCG2 axis | Degradation of AR is effective in suppressing OCSO subtype. |
Addie et al. (2019) | A2780, OV90, OVCAR3, OVCAR8, SKOV3, COV362.4 | Metformin/enzalutamide | AR→PI3K pathway | Anti-androgen failed to suppress AR+ EOC cells, implicating an ligand-independent pathway of AR. |
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Chung, W.-M.; Chen, L.; Chang, W.-C.; Su, S.-Y.; Hung, Y.-C.; Ma, W.-L. Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials. Int. J. Mol. Sci. 2021, 22, 7748. https://doi.org/10.3390/ijms22147748
Chung W-M, Chen L, Chang W-C, Su S-Y, Hung Y-C, Ma W-L. Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials. International Journal of Molecular Sciences. 2021; 22(14):7748. https://doi.org/10.3390/ijms22147748
Chicago/Turabian StyleChung, Wei-Min, Lumin Chen, Wei-Chun Chang, Sheng-Yuan Su, Yao-Ching Hung, and Wen-Lung Ma. 2021. "Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials" International Journal of Molecular Sciences 22, no. 14: 7748. https://doi.org/10.3390/ijms22147748