Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells

Authors

Ashley V. Huang, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
Yali Kong, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
Kan Wang, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
Milton L. Brown, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
David Mu, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow

ORCID

0009-0008-7575-2043 (Kong), 0009-0009-0489-8245 (Brown), 0000-0002-7762-0182 (Mu)

Document Type

Article

Publication Date

2025

DOI

10.3390/ijms26167935

Publication Title

International Journal of Molecular Sciences

Volume

26

Issue

16

Pages

7935

Abstract

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting BCSCs and expands on the challenges for the development of anti-BCSC drugs. We explore cutting-edge approaches like artificial intelligence (AI)-driven drug discovery and urge readers to seriously consider biological clocks and chronotherapy as experimental variables in drug discovery. Collectively, the task of cancer researchers is to overcome the many hurdles targeting BCSCs if we hope to tangibly improve breast cancer treatment outcomes and reduce mortality.

Rights

© 2025 by the authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "The datasets and materials used and/or analyzed during the current study are available from the corresponding author upon reasonable request."

Original Publication Citation

Huang, A. V., Kong, Y., Wang, K., Brown, M. L., & Mu, D. (2025). Protein marker-dependent drug discovery targeting breast cancer stem cells. International Journal of Molecular Sciences, 26(16), Article 7935. https://doi.org/10.3390/ijms26167935

Repository Citation

Huang, A. V., Kong, Y., Wang, K., Brown, M. L., & Mu, D. (2025). Protein marker-dependent drug discovery targeting breast cancer stem cells. International Journal of Molecular Sciences, 26(16), Article 7935. https://doi.org/10.3390/ijms26167935