Related Experiment Video
Updated: Nov 13, 2025
Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
A narrative review of proteolytic targeting chimeras (PROTACs): future perspective for prostate cancer therapy
Xuanrong Chen1, Haishan Shen2, Yi Shao1
1Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Abstract:
Proteolysis-TArgeting Chimeras (PROTACs) technology, as a strategy to chemically knock down transcription factors at the protein levels, can hijack the ubiquitin-proteasome degradation system to initiate the intracellular ubiquitin-proteasome hydrolysis process to degrade proteins. In the past, the development of drugs that target transcription factors has been greatly restricted, and even historically transcription factors have been regarded as "undruggable targets". PROTAC technology breaks through this limitation with its unique targeting design. With several generations of technical innovation, PROTACs have become more mature and continue to make breakthroughs in the field of targeted therapy including prostate cancer (PCa), with a new strategy for the development of anti-tumor targeted drugs. PROTACs have all the advantages of existing small molecule inhibitors, are easy to administer orally, have good cell permeability, and have wider targeting profiles compared to conventional inhibitors. The disadvantage of PROTACs is the noncancer specificity, off-target and sustained-release control, due to its catalytic role. Some androgen receptor (AR) and CDK4/6 degraders have advanced the field of PCa treatment, which is being further modified given the effects of these degraders in preclinical and clinical studies. This review summarizes in detail the technological progress and challenges that have been faced with PROTACs, the progress of research on PCa, and the prospective future of PROTACs development.
Insights
Proteolysis-TArgeting Chimeras (PROTACs) offer a novel approach to degrade transcription factors, overcoming previous "undruggable" limitations. This technology shows promise in prostate cancer treatment, with ongoing advancements and challenges being explored.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Transcription factors were historically considered undruggable targets for drug development.
- Proteolysis-TArgeting Chimeras (PROTACs) leverage the ubiquitin-proteasome system for targeted protein degradation.
- PROTAC technology presents a new strategy for developing anti-tumor targeted drugs.
Purpose of the Study:
- To review the technological progress and challenges of PROTACs.
- To summarize the advancements in PROTAC research for prostate cancer (PCa) treatment.
- To discuss the future prospects of PROTAC development in oncology.
Main Methods:
- Review of existing literature on PROTAC technology and its application in prostate cancer.
- Analysis of PROTAC advantages, disadvantages, and specific examples like AR and CDK4/6 degraders.
- Discussion of preclinical and clinical study outcomes.
Main Results:
- PROTACs overcome limitations of targeting transcription factors, offering advantages over small molecule inhibitors.
- Androgen receptor (AR) and CDK4/6 degraders have shown progress in preclinical and clinical studies for PCa.
- PROTACs exhibit potential for oral administration and broad targeting but face challenges in specificity and controlled release.
Conclusions:
- PROTAC technology represents a significant advancement in targeted therapy, particularly for prostate cancer.
- Further research and modification of PROTACs are necessary to address challenges like non-cancer specificity and controlled release.
- PROTACs hold considerable promise for future anti-tumor drug development.
