BCAR4 Expression as a Predictive Biomarker for Endocrine Therapy Resistance in Breast Cancer.

BACKGROUND: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer. PATIENTS AND METHODS: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 molecular subtypes. The relationship between elevated BCAR4 expression and resistance to endocrine therapy including AIs, the prevailing standard-of-care for endocrine therapy, was also investigated. RESULTS: This meta-analysis corroborated the link between BCAR4 expression and adverse outcomes as well as resistance to endocrine therapy in breast cancer. Notably, BCAR4 expression is clinically significant in luminal A and B subtypes. Additionally, an association between BCAR4 expression and resistance to AI treatment was discerned. CONCLUSION: This study expands on previous findings by demonstrating that BCAR4 expression is associated with resistance to newer therapies. The identification of patients with intrinsic resistance to hormone therapy is crucial to avoid ineffective treatment strategies. These findings contribute to our understanding of endocrine therapy resistance in breast cancer and could potentially guide the development of more effective treatment strategies.

Phosphoserine enhanced Cu-doped bioactive glass dynamic dual-network hydrogel for craniofacial bone defect repair.

Flexible hydrogels containing various osteogenic inorganic constituents, which can accommodate complicated shape variations, are considered as ideal grafts for craniofacial bone defect reconstruction. However, in most hybrid hydrogels, poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties, clinical manipulation and repair efficacy. In this article, we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass (CuBG) and phosphoserine (PS), in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked network. PS acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite hydrogels. The CuBG/PS hydrogels exhibited suitable rheological properties (injectable, self-healing, shape-adaptable), bone tissue integrating ability and anti-bacterial property. Meanwhile, we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo, particularly when the ratio of CuBG to PS is lower than 3 (9CB/3PS). This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.