AUTHOR=Chen Ruixian , Zhou Zhilan , Meng Xiangyue , Lei Yi , Wang Yuxi , Wang Yanyan 

TITLE=Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1578342

DOI=10.3389/fphar.2025.1578342

ISSN=1663-9812

ABSTRACT=Breast cancer is now the most common malignancy among females. Numerous highly effective small-molecule inhibitors, such as tamoxifen and fulvestrant, have received clinical approval, significantly enhancing the therapeutic landscape of breast cancer. However, the emergence of drug resistance in some patients presents an unmet clinical need. Identifying resistance-related targets has been a key therapeutic strategy in combating drug-resistant tumors. Studies investigating the molecular characteristics and resistance mechanisms of breast cancer have unveiled novel targets, including cell cycle checkpoint molecules, breast cancer stem cell-related molecules, and anti-apoptotic proteins. Relevant small-molecule inhibitors have shown promising potential in overcoming drug-resistant breast cancer in both preclinical and clinical trials. In this review, we evaluate the resistance mechanisms of available targeted inhibitors for breast cancer and summarize innovative targeted strategies with the potential to overcome resistance, guided by clinical research.