PROTACs in Ovarian Cancer: Current Advancements and Future Perspectives

Makenzie Vorderbruggen, Carlos A. Velázquez-Martínez, Amarnath Natarajan, Adam R. Karpf

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Ovarian cancer is the deadliest gynecologic malignancy. The majority of patients diagnosed with advanced ovarian cancer will relapse, at which point additional therapies can be administered but, for the most part, these are not curative. As such, a need exists for the development of novel therapeutic options for ovarian cancer patients. Research in the field of targeted protein degradation (TPD) through the use of proteolysis-targeting chimeras (PROTACs) has significantly increased in recent years. The ability of PROTACs to target proteins of interest (POI) for degradation, overcoming limitations such as the incomplete inhibition of POI function and the development of resistance seen with other inhibitors, is of particular interest in cancer research, including ovarian cancer research. This review provides a synopsis of PROTACs tested in ovarian cancer models and highlights PROTACs characterized in other types of cancers with potential high utility in ovarian cancer. Finally, we discuss methods that will help to enable the selective delivery of PROTACs to ovarian cancer and improve the pharmacodynamic properties of these agents.

Original languageEnglish (US)
Article number5067
JournalInternational journal of molecular sciences
Volume25
Issue number10
DOIs
StatePublished - May 2024

Keywords

  • PROTAC
  • high-grade serous ovarian cancer
  • ovarian cancer
  • targeted protein degradation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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