PROTACs in the Management of Prostate Cancer
Cancer treatments with targeted therapy have gained immense interest due to their low levels of toxicity and high selectivity. Proteolysis-Targeting Chimeras (PROTACs) have drawn special attention in the development of cancer therapeutics owing to their unique mechanism of action, their ability to t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/9/3698 |
| _version_ | 1827742852995612672 |
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| author | Poornachandra Yedla Ahmed O. Babalghith Vindhya Vasini Andra Riyaz Syed |
| author_facet | Poornachandra Yedla Ahmed O. Babalghith Vindhya Vasini Andra Riyaz Syed |
| author_sort | Poornachandra Yedla |
| collection | DOAJ |
| description | Cancer treatments with targeted therapy have gained immense interest due to their low levels of toxicity and high selectivity. Proteolysis-Targeting Chimeras (PROTACs) have drawn special attention in the development of cancer therapeutics owing to their unique mechanism of action, their ability to target undruggable proteins, and their focused target engagement. PROTACs selectively degrade the target protein through the ubiquitin–proteasome system, which describes a different mode of action compared to conventional small-molecule inhibitors or even antibodies. Among different cancer types, prostate cancer (PC) is the most prevalent non-cutaneous cancer in men. Genetic alterations and the overexpression of several genes, such as FOXA1, AR, PTEN, RB1, TP53, etc., suppress the immune response, resulting in drug resistance to conventional drugs in prostate cancer. Since the progression of ARV-110 (PROTAC for PC) into clinical phases, the focus of research has quickly shifted to protein degraders targeting prostate cancer. The present review highlights an overview of PROTACs in prostate cancer and their superiority over conventional inhibitors. We also delve into the underlying pathophysiology of the disease and explain the structural design and linkerology strategies for PROTAC molecules. Additionally, we touch on the various targets for PROTAC in prostate cancer, including the androgen receptor (AR) and other critical oncoproteins, and discuss the future prospects and challenges in this field. |
| first_indexed | 2024-03-11T04:12:13Z |
| format | Article |
| id | doaj.art-737f3380b8d24a9a83f37e9e11f5c5f6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:12:13Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-737f3380b8d24a9a83f37e9e11f5c5f62023-11-17T23:22:15ZengMDPI AGMolecules1420-30492023-04-01289369810.3390/molecules28093698PROTACs in the Management of Prostate CancerPoornachandra Yedla0Ahmed O. Babalghith1Vindhya Vasini Andra2Riyaz Syed3Department of Pharmacogenomics, Institute of Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology Hospitals, Gachibowli, Hyderabad 500082, IndiaDepartment of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Medical Oncology, Omega Hospitals, Gachibowli, Hyderabad 500032, IndiaDepartment of Chemiinformatics, Centella Scientific, JHUB, Jawaharlal Nehru Technological University, Hyderabad 500085, IndiaCancer treatments with targeted therapy have gained immense interest due to their low levels of toxicity and high selectivity. Proteolysis-Targeting Chimeras (PROTACs) have drawn special attention in the development of cancer therapeutics owing to their unique mechanism of action, their ability to target undruggable proteins, and their focused target engagement. PROTACs selectively degrade the target protein through the ubiquitin–proteasome system, which describes a different mode of action compared to conventional small-molecule inhibitors or even antibodies. Among different cancer types, prostate cancer (PC) is the most prevalent non-cutaneous cancer in men. Genetic alterations and the overexpression of several genes, such as FOXA1, AR, PTEN, RB1, TP53, etc., suppress the immune response, resulting in drug resistance to conventional drugs in prostate cancer. Since the progression of ARV-110 (PROTAC for PC) into clinical phases, the focus of research has quickly shifted to protein degraders targeting prostate cancer. The present review highlights an overview of PROTACs in prostate cancer and their superiority over conventional inhibitors. We also delve into the underlying pathophysiology of the disease and explain the structural design and linkerology strategies for PROTAC molecules. Additionally, we touch on the various targets for PROTAC in prostate cancer, including the androgen receptor (AR) and other critical oncoproteins, and discuss the future prospects and challenges in this field.https://www.mdpi.com/1420-3049/28/9/3698PROTACprostate cancerandrogen receptormutationresistance |
| spellingShingle | Poornachandra Yedla Ahmed O. Babalghith Vindhya Vasini Andra Riyaz Syed PROTACs in the Management of Prostate Cancer Molecules PROTAC prostate cancer androgen receptor mutation resistance |
| title | PROTACs in the Management of Prostate Cancer |
| title_full | PROTACs in the Management of Prostate Cancer |
| title_fullStr | PROTACs in the Management of Prostate Cancer |
| title_full_unstemmed | PROTACs in the Management of Prostate Cancer |
| title_short | PROTACs in the Management of Prostate Cancer |
| title_sort | protacs in the management of prostate cancer |
| topic | PROTAC prostate cancer androgen receptor mutation resistance |
| url | https://www.mdpi.com/1420-3049/28/9/3698 |
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