BRCA1 deficiency in triple-negative breast cancer: Protein stability as a basis for therapy

Eun Choi, Gil im Mun, Joohyun Lee, Hanhee Lee, Jaeho Cho, Yun Sil Lee

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Mutations in breast cancer-associated 1 (BRCA1) increase the lifetime risk of developing breast cancer by up to 51% over the risk of the general population. Many aspects of this multifunctional protein have been revealed, including its essential role in homologous recombination repair, E3 ubiquitin ligase activity, transcriptional regulation, and apoptosis. Although most studies have focused on BRCA1 deficiency due to mutations, only a minority of patients carry BRCA1 mutations. A recent study has suggested an expanded definition of BRCA1 deficiency with reduced BRCA1 levels, which accounts for almost half of all triple-negative breast cancer (TNBC) patients. Reduced BRCA1 levels can result from epigenetic modifications or increased proteasomal degradation. In this review, we discuss how this knowledge of BRCA1 function and regulation of BRCA1 protein stability can help overcome the challenges encountered in the clinic and advance current treatment strategies for BRCA1-related breast cancer patients, especially focusing on TNBC.

Original languageEnglish
Article number114090
JournalBiomedicine and Pharmacotherapy
Volume158
DOIs
StatePublished - Feb 2023

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants ( NRF-2020R1A2C3013255 2018R1A5A2025286 and 2020M2D9A2093974 ), funded by the Korea government (Ministry of Science and ICT). The authors thank Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work.

Publisher Copyright:
© 2022 The Authors

Keywords

  • BRCA1 deficiency
  • Chemotherapy resistance
  • Multifunction
  • Proteasomal degradation
  • Triple-negative breast cancer

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