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Targeting micro-environmental pathways by PROTACs as a therapeutic strategy

Jing Liu1, Yunhua Peng1, Hiroyuki Inuzuka1

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.

Seminars in Cancer Biology
|July 7, 2022
PubMed

Insights

PROteolysis-TArgeting Chimeras (PROTACs) offer a novel approach to cancer treatment by targeting the tumor microenvironment (TME). This review highlights PROTAC development against TME pathways for overcoming drug resistance and advancing cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • The tumor microenvironment (TME) comprises diverse cellular and non-cellular elements that foster tumor growth, metastasis, and immune evasion.
  • The TME also contributes significantly to therapeutic resistance, limiting the efficacy of conventional treatments.
  • Small molecule inhibitors (SMIs) and antibodies targeting TME components are established cancer treatment strategies.

Purpose of the Study:

  • To review recent advancements in PROteolysis-TArgeting Chimera (PROTAC) development targeting the tumor microenvironment (TME).
  • To explore the advantages of PROTACs over traditional therapies, particularly in overcoming drug resistance.
  • To propose future directions for PROTAC technology in cancer treatment.

Main Methods:

  • Literature review of recent studies on PROTACs targeting TME pathways.
  • Analysis of PROTAC mechanisms, advantages, and limitations compared to SMIs and antibodies.
  • Synthesis of current progress and future perspectives in PROTAC-based cancer therapy.

Main Results:

  • PROTACs demonstrate significant potential in targeting specific components within the TME.
  • PROTACs offer a promising strategy to overcome resistance mechanisms associated with conventional cancer therapies.
  • Numerous PROTACs targeting TME pathways are under active development for cancer treatment.

Conclusions:

  • PROTAC technology represents a promising frontier in cancer therapy, particularly for targeting the complex TME.
  • Further development of PROTACs holds the potential to overcome existing therapeutic challenges and improve patient outcomes.
  • Future research should focus on optimizing PROTAC design and delivery for enhanced efficacy against TME-driven cancers.
Keywords:
Cancer stem cellImmunotherapyMetabolismPRoteolysis-TArgeting Chimeras (PROTAC)

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