Investigating the Anti-Cancer Mechanism of Targeting Udp-Glucuronosyltransferase 2b7 (Ugt-2b7) through Multigenerational Breast Cancer Metastasis Animal Model and Genome-Wide Crispr-Cas9 Knock out (Gecko) Screening Model.

reast cancer has consistently ranked as the most prevalent cancer among women in Taiwan, with its incidence rate consistently among the top three in cancer growth over the past five years. Despite advancements in chemotherapy and radiotherapy that have significantly improved the five-year survival rate for early-stage breast cancer, treatment options remain limited for the highly ggressive triplenegative breast cancer (TNBC) subtype. TNBC patients face elevated risks of recurrence and metastasis post-surgery. Although an antibody-drug conjugate, IMMU-132, has recently been approved for advanced TNBC, its application remains limited, leaving the majority of TNBC patients with few effective therapeutic options. As such, developing novel targeted therapies and metastasis prevention strategies for TNBC has become a critical focus in breast cancer research. Based on previous research achievements, this project has successfully established a high-metastasis breast cancer animal model, elucidated metastasis mechanisms, and identified unique biomarkers, confirming the pivotal role of UDP-glucuronosyltransferase 2B7 (UGT2B7) in cancer metastasis and cancer stem cell function. Additionally, a comprehensive genome-wide CRISPR knockout (GeCKO) research platform was developed, integrated with the high-metastasisbreast cancer model, leading to the iscovery of several candidate genes with substantial anti-cancer potential and clinical relevance. High-throughput tissue array analysis has further validated the correlation between UGT2B7 expression and the proximal and distal metastatic
capabilities of breast tumors. Our recent international collaborative publication with Australia highlighted the substantial anti-cancer potential of epidermal growth factor receptor (EGFR) in TNBC therapy, with our project demonstrating that EGFR-targeted therapy can effectively suppress high-metastasis breast cancer proliferation. In the next phase, we will pursue gene editing approaches
targeting UGT2B7 and other potential anti-cancer targets, along with oncogenic genes identified through the GeCKO platform, to drive clinical applications of innovative anti-breast cancer and anti-metastasis therapies.