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PROTACS- targeted protein degradation as a path to precision cancer therapeutics

Hannah R Gatley1, Paul B Fisher1, Swadesh K Das1

  • 1Department of Cellular, Molecular and Genetic Medicine, VCU Institute of Molecular Medicine, VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Virginia, United States.

Advances in Cancer Research
|November 16, 2025
PubMed

Insights

Proteolysis-Targeting Chimeras (PROTACs) offer a novel therapeutic strategy for cancer by degrading disease-causing proteins. This targeted protein degradation approach is expanding research for both

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer treatment requires novel strategies, including targeted protein degradation.
  • Proteolysis-Targeting Chimeras (PROTACs) represent a new therapeutic modality.
  • PROTACs leverage the ubiquitin-proteasome system for targeted protein destruction.

Purpose of the Study:

  • To review the emerging field of PROTAC technology in cancer management.
  • To highlight the mechanism and potential of PROTACs in targeting disease-causing proteins.
  • To discuss the expansion of PROTAC research in academia and industry.

Main Methods:

  • Review of scientific literature on PROTAC technology.
  • Analysis of PROTAC mechanisms targeting the ubiquitin-proteasome system.
  • Evaluation of PROTAC applications across various cancer types.

Main Results:

  • PROTACs offer a versatile molecular structure adaptable to specific protein targets.
  • The technology effectively targets a broad spectrum of proteins, including previously 'undruggable' ones.
  • PROTACs have shown efficacy in diverse cancer variants by degrading key proteins.

Conclusions:

  • PROTAC technology represents a significant advancement in targeted protein degradation for cancer therapy.
  • The ability to degrade both 'druggable' and 'undruggable' targets fuels rapid research expansion.
  • Further development is crucial for translating PROTACs into clinical applications for dynamic protein management.
Keywords:
CancerProteolysis-targeting chimera (PROTAC)Ubiquitin-proteasome system (UPS)

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