Therapeutic Approaches to Targeting Androgen Receptor Splice Variants
Therapeutic options for advanced prostate cancer have vastly expanded over the last decade and will continue to expand in the future. Drugs targeting the androgen receptor (AR) signaling pathway, i.e., androgen receptor targeting agents (ARTAs), remain the mainstream treatments that are increasingly...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/1/104 |
| _version_ | 1797358998915121152 |
|---|---|
| author | Violet A. Daniels Jun Luo Channing J. Paller Mayuko Kanayama |
| author_facet | Violet A. Daniels Jun Luo Channing J. Paller Mayuko Kanayama |
| author_sort | Violet A. Daniels |
| collection | DOAJ |
| description | Therapeutic options for advanced prostate cancer have vastly expanded over the last decade and will continue to expand in the future. Drugs targeting the androgen receptor (AR) signaling pathway, i.e., androgen receptor targeting agents (ARTAs), remain the mainstream treatments that are increasingly transforming the disease into one that can be controlled for an extended period of time. Prostate cancer is inherently addicted to AR. Under the treatment pressure of ARTA, molecular alterations occur, leading to the clonal expansion of resistant cells in a disease state broadly categorized as castration-resistant prostate cancer (CRPC). One castration resistance mechanism involves AR splice variants (AR-Vs) lacking the ligand-binding domain. Some AR-Vs have been identified as constitutively active, capable of activating AR signaling pathways without androgenic ligands. Among these variants, AR-V7 is the most extensively studied and may be measured non-invasively using validated circulating tumor cell (CTC) tests. In the context of the evolving prostate cancer treatment landscape, novel agents are developed and evaluated for their efficacy in targeting AR-V7. In patients with metastatic CRPC (mCRPC), the availability of the AR-V7 tests will make it possible to determine whether the treatments are effective for CTC AR-V7-positive disease, even though the treatments may not be specifically designed to target AR-V7. In this review, we will first outline the current prostate cancer treatment landscape, followed by an in-depth review of relatively newer prostate cancer therapeutics, focusing on AR-targeting agents under clinical development. These drugs are categorized from the standpoint of their activities against AR-V7 through direct or indirect mechanisms. |
| first_indexed | 2024-03-08T15:09:18Z |
| format | Article |
| id | doaj.art-51bbd29efee7411c9bf3ef459604643b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T15:09:18Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-51bbd29efee7411c9bf3ef459604643b2024-01-10T14:53:33ZengMDPI AGCells2073-44092024-01-0113110410.3390/cells13010104Therapeutic Approaches to Targeting Androgen Receptor Splice VariantsViolet A. Daniels0Jun Luo1Channing J. Paller2Mayuko Kanayama3Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartments of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USATherapeutic options for advanced prostate cancer have vastly expanded over the last decade and will continue to expand in the future. Drugs targeting the androgen receptor (AR) signaling pathway, i.e., androgen receptor targeting agents (ARTAs), remain the mainstream treatments that are increasingly transforming the disease into one that can be controlled for an extended period of time. Prostate cancer is inherently addicted to AR. Under the treatment pressure of ARTA, molecular alterations occur, leading to the clonal expansion of resistant cells in a disease state broadly categorized as castration-resistant prostate cancer (CRPC). One castration resistance mechanism involves AR splice variants (AR-Vs) lacking the ligand-binding domain. Some AR-Vs have been identified as constitutively active, capable of activating AR signaling pathways without androgenic ligands. Among these variants, AR-V7 is the most extensively studied and may be measured non-invasively using validated circulating tumor cell (CTC) tests. In the context of the evolving prostate cancer treatment landscape, novel agents are developed and evaluated for their efficacy in targeting AR-V7. In patients with metastatic CRPC (mCRPC), the availability of the AR-V7 tests will make it possible to determine whether the treatments are effective for CTC AR-V7-positive disease, even though the treatments may not be specifically designed to target AR-V7. In this review, we will first outline the current prostate cancer treatment landscape, followed by an in-depth review of relatively newer prostate cancer therapeutics, focusing on AR-targeting agents under clinical development. These drugs are categorized from the standpoint of their activities against AR-V7 through direct or indirect mechanisms.https://www.mdpi.com/2073-4409/13/1/104androgen receptor splice variantsAR-V7castration-resistant prostate cancer |
| spellingShingle | Violet A. Daniels Jun Luo Channing J. Paller Mayuko Kanayama Therapeutic Approaches to Targeting Androgen Receptor Splice Variants Cells androgen receptor splice variants AR-V7 castration-resistant prostate cancer |
| title | Therapeutic Approaches to Targeting Androgen Receptor Splice Variants |
| title_full | Therapeutic Approaches to Targeting Androgen Receptor Splice Variants |
| title_fullStr | Therapeutic Approaches to Targeting Androgen Receptor Splice Variants |
| title_full_unstemmed | Therapeutic Approaches to Targeting Androgen Receptor Splice Variants |
| title_short | Therapeutic Approaches to Targeting Androgen Receptor Splice Variants |
| title_sort | therapeutic approaches to targeting androgen receptor splice variants |
| topic | androgen receptor splice variants AR-V7 castration-resistant prostate cancer |
| url | https://www.mdpi.com/2073-4409/13/1/104 |
| work_keys_str_mv | AT violetadaniels therapeuticapproachestotargetingandrogenreceptorsplicevariants AT junluo therapeuticapproachestotargetingandrogenreceptorsplicevariants AT channingjpaller therapeuticapproachestotargetingandrogenreceptorsplicevariants AT mayukokanayama therapeuticapproachestotargetingandrogenreceptorsplicevariants |