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Targeting Oncoproteins for Degradation by Small Molecule-Based Proteolysis-Targeting Chimeras (PROTACs) in Sex

Li Liu1,2, Lihong Shi1, Zhaodi Wang3

  • 1Department of Clinical Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Frontiers in Endocrinology
|April 4, 2022
PubMed

Insights

Proteolysis-targeting chimeras (PROTACs) offer a new way to degrade proteins driving hormone-dependent cancers like breast and prostate cancer. This novel approach may overcome resistance to current endocrine therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Sex hormone-dependent cancers (breast, ovarian, prostate) are a major cause of cancer mortality worldwide.
  • Steroid hormones mediate tumor growth via receptors like estrogen receptors (ERs) and androgen receptors (ARs).
  • Targeting these receptors with endocrine therapy is a key strategy, but resistance is a challenge.

Purpose of the Study:

  • To introduce the proteolysis-targeting chimera (PROTAC) strategy.
  • To review the progress of small molecule PROTACs targeting oncoproteins in sex hormone-dependent cancers.
  • To highlight PROTACs' potential to overcome endocrine therapy resistance.

Main Methods:

  • Review of existing literature on PROTAC technology.
  • Summary of PROTAC development for targeting ERs, ARs, and ERRs.
  • Focus on applications in breast and prostate cancer treatment.

Main Results:

  • PROTACs utilize the ubiquitin-proteasome system to degrade target proteins.
  • Small molecule PROTACs have shown efficacy in preclinical and clinical studies.
  • PROTACs targeting key receptors in hormone-dependent cancers are emerging.

Conclusions:

  • PROTACs represent a promising therapeutic modality for hormone-dependent cancers.
  • This approach offers a potential solution to overcome resistance to conventional endocrine therapies.
  • Further development of PROTACs could revolutionize treatment for breast and prostate cancers.
Keywords:
PROTACsandrogen receptorsestrogen receptorssex hormone-dependent cancerssmall molecule inhibitors

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