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PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review

Chao Wang1, Yujing Zhang2, Wanpeng Yu3

  • 1Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, Shandong, China.

International Journal of Biological Macromolecules
|February 1, 2024
PubMed

Insights

Proteolysis targeting chimera (PROTAC) technology shows promise for targeted protein degradation. PROTAC-biomacromolecule conjugates (PBCs) enhance targetability and reduce toxicity, paving the way for safer cancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Proteolysis targeting chimera (PROTAC) technology offers a novel approach to targeted protein degradation with significant therapeutic potential.
  • A major challenge for clinical application, particularly in cancer therapy, is on-target, off-tumour toxicity in healthy cells.
  • Optimizing degradation activity and cellular selectivity is crucial to minimize undesirable side effects.

Purpose of the Study:

  • To review recent advances in PROTAC-biomacromolecule conjugates (PBCs).
  • To discuss current challenges associated with PBCs.
  • To outline future research opportunities in the field of targeted protein degradation.

Main Methods:

  • Review of recent scientific literature on PROTAC technology and biomacromolecule conjugates.
  • Analysis of strategies combining PROTACs with biomacromolecules like antibodies and aptamers.
  • Synthesis of information regarding the development and application of PROTAC-biomacromolecule conjugates (PBCs).

Main Results:

  • PROTAC-antibody conjugates and PROTAC-aptamer conjugates represent innovative approaches.
  • These PROTAC-biomacromolecule conjugates (PBCs) demonstrate enhanced targetability of PROTACs.
  • PBCs show potential in reducing off-target side effects, improving safety profiles.

Conclusions:

  • The combination of potent PROTACs and safe biomacromolecules is a pioneering trend in targeted protein degradation.
  • PROTAC-biomacromolecule conjugates (PBCs) offer a promising strategy to overcome the toxicity challenges of PROTAC technology.
  • Further research into PBCs holds significant opportunities for advancing cancer therapy and other disease treatments.
Keywords:
BiomacromoleculeCancer therapyPBCsPROTACs

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