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Protacs in cancer therapy: mechanisms, design, clinical trials, and future directions

Akash Vikal1, Rashmi Maurya1, Brij Bihari Patel2

  • 1Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga, 142001, Punjab, India.

Drug Delivery and Translational Research
|November 29, 2024
PubMed

Insights

Proteolysis-Targeting Chimeras (PROTACs) offer a novel approach to cancer therapy by degrading disease-causing proteins. This review highlights PROTACs

Area of Science:

  • Oncology and Molecular Biology
  • Drug Discovery and Development
  • Biochemistry and Proteomics

Background:

  • Cancer arises from genetic and epigenetic alterations, activating oncogenes and silencing tumor suppressors.
  • Current cancer treatments (chemotherapy, radiotherapy, surgery) have limitations, including significant side effects and modest survival benefits.
  • There is a critical need for novel, effective cancer therapies with improved safety profiles.

Purpose of the Study:

  • To review the emerging role of Proteolysis-Targeting Chimeras (PROTACs) as a transformative therapeutic strategy in oncology.
  • To provide a comprehensive overview of PROTAC technology, including its mechanism, design, and application in targeting oncogenic proteins.
  • To discuss the current challenges, advancements, and future prospects of PROTACs in cancer treatment.

Main Methods:

  • Literature review focusing on Proteolysis-Targeting Chimeras (PROTACs) in cancer therapy.
  • Analysis of PROTACs' mechanism of action, molecular design principles, and structure-activity relationships.
  • Exploration of nanotechnology applications, clinical trial progress, and patent landscape related to PROTACs.

Main Results:

  • PROTACs leverage the ubiquitin-proteasome system to selectively degrade target proteins, offering a precise therapeutic modality.
  • The review details the historical development, design considerations, and specific targeting of oncogenic proteins by PROTACs.
  • Promising results from ongoing clinical trials indicate significant progress and potential for PROTAC-based cancer therapies.

Conclusions:

  • PROTACs represent a groundbreaking approach in targeted cancer therapy, offering a new paradigm for drug development.
  • Continued research and clinical trials are crucial for realizing the full potential of PROTACs in treating various cancers.
  • PROTAC technology holds significant promise for addressing dysregulated protein expression and improving patient outcomes in oncology and beyond.
Keywords:
Cancer targetingClinical trialsNanotechnologyPROTACsProtein of interestUbiquitin E3 ligase

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