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PROTAC as a novel anti-cancer strategy by targeting aging-related signaling

Yunhua Peng1, Donghua Liu2, Daoyuan Huang3

  • 1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

Seminars in Cancer Biology
|October 5, 2024
PubMed

Insights

Targeted protein degradation using Proteolysis-Targeting Chimeras (PROTACs) offers a novel therapeutic strategy for aging and cancer. PROTACs degrade disease-causing proteins, addressing shared hallmarks like cellular senescence and genomic instability.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology
  • Gerontology

Background:

  • Aging and cancer share common cellular hallmarks, including senescence, genomic instability, and dysregulated cell death/proliferation.
  • These shared pathways present opportunities for developing unified therapeutic interventions.
  • Targeted protein degradation is an emerging technology with potential applications in these areas.

Purpose of the Study:

  • To summarize recent advancements in Proteolysis-Targeting Chimeras (PROTACs) for targeting proteins implicated in cancer and aging.
  • To explore the potential of PROTACs in addressing shared cellular hallmarks of aging and cancer.
  • To discuss future perspectives for integrating PROTAC technology into cancer therapeutics.

Main Methods:

  • Review of recent scientific literature on PROTAC technology.
  • Analysis of PROTACs' mechanism of action involving the ubiquitin-proteasome system.
  • Identification of critical proteins targeted by PROTACs in cancer and aging models.

Main Results:

  • PROTACs effectively leverage the ubiquitin-proteasome system for targeted protein degradation.
  • Specific pathogenic proteins driving cancer progression and aging-related dysfunction can be degraded by PROTACs.
  • PROTACs demonstrate potential in addressing key oncogenic drivers and aging cellular pathologies.

Conclusions:

  • PROTACs represent a promising therapeutic modality for diseases characterized by protein aggregation or overexpression.
  • Targeting shared pathways in cancer and aging with PROTACs could lead to more effective treatments.
  • Further research and development are warranted to fully realize the clinical potential of PROTACs in oncology and gerontology.
Keywords:
Cancer therapyPROteolysis-TArgeting Chimera (PROTAC)Protein degradationSenescence

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