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Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy

Yujeong Moon1,2, Seong Ik Jeon3, Man Kyu Shim2

  • 1Department of Bioengineering, Korea University, Seoul 02841, Republic of Korea.

Pharmaceutics
|February 25, 2023
PubMed

Insights

Proteolysis-targeting chimeras (PROTACs) offer a novel cancer therapy by degrading oncogenic proteins. Enhancing their delivery systems is crucial for improving pharmacokinetic properties and efficacy in cancer immunotherapy.

Area of Science:

  • Oncology
  • Biochemistry
  • Drug Delivery

Background:

  • Proteolysis-targeting chimeras (PROTACs) are emerging therapeutics for cancer, inducing targeted protein degradation.
  • PROTACs leverage the ubiquitin-proteasome system to eliminate oncogenic proteins, offering advantages over traditional inhibitors.
  • Their application is expanding into cancer immunotherapy by targeting proteins within the tumor microenvironment.

Purpose of the Study:

  • To review the characteristics, development, and pharmacokinetic properties of PROTACs.
  • To explore the application of various delivery systems for PROTACs in cancer immunotherapy.
  • To summarize recent advancements in PROTAC drug delivery for enhanced therapeutic outcomes.

Main Methods:

  • Review of existing literature on PROTACs and drug delivery systems.
  • Analysis of passive and active targeting strategies for PROTAC delivery.
  • Evaluation of the impact of delivery systems on PROTAC pharmacokinetics and tumor targeting.

Main Results:

  • PROTACs demonstrate potential for treating cancers by degrading specific oncogenic proteins.
  • Poor solubility and cell permeability of PROTACs necessitate advanced delivery systems.
  • Targeted delivery systems can improve PROTAC pharmacokinetics and tumor accumulation.

Conclusions:

  • Optimized delivery systems are essential for advancing PROTACs in cancer therapy and immunotherapy.
  • Effective drug delivery strategies are key to overcoming PROTAC limitations and improving clinical translation.
  • PROTACs, when coupled with appropriate delivery systems, hold significant promise for future cancer treatments.
Keywords:
cancer immunotherapycancer-targeted therapydrug delivery systemprotein degradationproteolysis-targeting chimera (PROTAC)

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