Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy
- 주제(키워드) proteolysis-targeting chimera (PROTAC) , protein degradation , drug delivery system , cancer-targeted therapy , cancer immunotherapy
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Moon, Yujeong] Korea Univ, Dept Bioengn, Seoul 02841, South Korea; [Moon, Yujeong; Shim, Man Kyu] Korea Inst Sci & Technol KIST, Biomed Res Inst, Seoul 02792, South Korea; [Jeon, Seong Ik; Kim, Kwangmeyung] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 MDPI
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000204275
- 본문언어 영어
- Published As https://doi.org/10.3390/pharmaceutics15020411
초록/요약
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.
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