Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy
Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utiliz...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/411 |
| _version_ | 1797618722679029760 |
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| author | Yujeong Moon Seong Ik Jeon Man Kyu Shim Kwangmeyung Kim |
| author_facet | Yujeong Moon Seong Ik Jeon Man Kyu Shim Kwangmeyung Kim |
| author_sort | Yujeong Moon |
| collection | DOAJ |
| description | Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utilizing the ubiquitin-proteasome pathway. Since their mode of action is universal, irreversible, recyclable, long-lasting, and applicable to ‘undruggable’ proteins, PROTACs are gradually replacing the role of conventional small molecular inhibitors. Moreover, their application areas are being expanded to cancer immunotherapy as various types of oncogenic proteins that are involved in immunosuppressive tumor microenvironments. However, poor water solubility and low cell permeability considerably restrict the pharmacokinetic (PK) property, which necessitates the use of appropriate delivery systems for cancer immunotherapy. In this review, the general characteristics, developmental status, and PK of PROTACs are first briefly covered. Next, recent studies on the application of various types of passive or active targeting delivery systems for PROTACs are introduced, and their effects on the PK and tumor-targeting ability of PROTACs are described. Finally, recent drug delivery systems of PROTACs for cancer immunotherapy are summarized. The adoption of an adequate delivery system for PROTAC is expected to accelerate the clinical translation of PROTACs, as well as improve its efficacy for cancer therapy. |
| first_indexed | 2024-03-11T08:16:26Z |
| format | Article |
| id | doaj.art-07645e52af67404cb7aae6ac8d893c8e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:16:26Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-07645e52af67404cb7aae6ac8d893c8e2023-11-16T22:39:36ZengMDPI AGPharmaceutics1999-49232023-01-0115241110.3390/pharmaceutics15020411Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer ImmunotherapyYujeong Moon0Seong Ik Jeon1Man Kyu Shim2Kwangmeyung Kim3Department of Bioengineering, Korea University, Seoul 02841, Republic of KoreaGraduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Woman’s University, Seoul 03760, Republic of KoreaBiomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaGraduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Woman’s University, Seoul 03760, Republic of KoreaProteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utilizing the ubiquitin-proteasome pathway. Since their mode of action is universal, irreversible, recyclable, long-lasting, and applicable to ‘undruggable’ proteins, PROTACs are gradually replacing the role of conventional small molecular inhibitors. Moreover, their application areas are being expanded to cancer immunotherapy as various types of oncogenic proteins that are involved in immunosuppressive tumor microenvironments. However, poor water solubility and low cell permeability considerably restrict the pharmacokinetic (PK) property, which necessitates the use of appropriate delivery systems for cancer immunotherapy. In this review, the general characteristics, developmental status, and PK of PROTACs are first briefly covered. Next, recent studies on the application of various types of passive or active targeting delivery systems for PROTACs are introduced, and their effects on the PK and tumor-targeting ability of PROTACs are described. Finally, recent drug delivery systems of PROTACs for cancer immunotherapy are summarized. The adoption of an adequate delivery system for PROTAC is expected to accelerate the clinical translation of PROTACs, as well as improve its efficacy for cancer therapy.https://www.mdpi.com/1999-4923/15/2/411proteolysis-targeting chimera (PROTAC)protein degradationdrug delivery systemcancer-targeted therapycancer immunotherapy |
| spellingShingle | Yujeong Moon Seong Ik Jeon Man Kyu Shim Kwangmeyung Kim Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy Pharmaceutics proteolysis-targeting chimera (PROTAC) protein degradation drug delivery system cancer-targeted therapy cancer immunotherapy |
| title | Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy |
| title_full | Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy |
| title_fullStr | Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy |
| title_full_unstemmed | Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy |
| title_short | Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy |
| title_sort | cancer specific delivery of proteolysis targeting chimeras protacs and their application to cancer immunotherapy |
| topic | proteolysis-targeting chimera (PROTAC) protein degradation drug delivery system cancer-targeted therapy cancer immunotherapy |
| url | https://www.mdpi.com/1999-4923/15/2/411 |
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