Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamid...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/9/6/67 |
| _version_ | 1797761336193581056 |
|---|---|
| author | Daniel J. Crona Young E. Whang |
| author_facet | Daniel J. Crona Young E. Whang |
| author_sort | Daniel J. Crona |
| collection | DOAJ |
| description | Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease. Mechanisms underlying progression to mCRPC and treatment resistance are extremely complex. AR-dependent resistance mechanisms include AR amplification, AR point mutations, expression of constitutively active AR splice variants, and altered intratumoral androgen biosynthesis. AR-independent resistance mechanisms include glucocorticoid receptor activation, immune-mediated resistance, and neuroendocrine differentiation. The development of novel agents, such as seviteronel, apalutamide, and EPI-001/EPI-506, as well as the identification and validation of novel predictive biomarkers of resistance, may lead to improved therapeutics for mCRPC patients. |
| first_indexed | 2024-03-12T19:11:30Z |
| format | Article |
| id | doaj.art-cd3451109ef049839bee38c89a34943e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:11:30Z |
| publishDate | 2017-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cd3451109ef049839bee38c89a34943e2023-08-02T05:54:44ZengMDPI AGCancers2072-66942017-06-01966710.3390/cancers9060067cancers9060067Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy ResistanceDaniel J. Crona0Young E. Whang1Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USALineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USADespite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease. Mechanisms underlying progression to mCRPC and treatment resistance are extremely complex. AR-dependent resistance mechanisms include AR amplification, AR point mutations, expression of constitutively active AR splice variants, and altered intratumoral androgen biosynthesis. AR-independent resistance mechanisms include glucocorticoid receptor activation, immune-mediated resistance, and neuroendocrine differentiation. The development of novel agents, such as seviteronel, apalutamide, and EPI-001/EPI-506, as well as the identification and validation of novel predictive biomarkers of resistance, may lead to improved therapeutics for mCRPC patients.http://www.mdpi.com/2072-6694/9/6/67castration-resistant prostate cancerandrogen receptorprogressionresistance mechanismsenzalutamideabiraterone |
| spellingShingle | Daniel J. Crona Young E. Whang Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance Cancers castration-resistant prostate cancer androgen receptor progression resistance mechanisms enzalutamide abiraterone |
| title | Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance |
| title_full | Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance |
| title_fullStr | Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance |
| title_full_unstemmed | Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance |
| title_short | Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance |
| title_sort | androgen receptor dependent and independent mechanisms involved in prostate cancer therapy resistance |
| topic | castration-resistant prostate cancer androgen receptor progression resistance mechanisms enzalutamide abiraterone |
| url | http://www.mdpi.com/2072-6694/9/6/67 |
| work_keys_str_mv | AT danieljcrona androgenreceptordependentandindependentmechanismsinvolvedinprostatecancertherapyresistance AT youngewhang androgenreceptordependentandindependentmechanismsinvolvedinprostatecancertherapyresistance |