Review Article: Decoding the Role of PBX3 in Cancer: Molecular Mechanisms and Therapeutic Strategies

Pre-B-cell leukemia homeobox 3 (PBX3) is a homeobox transcription factor that belongs to the pre-B-cell leukemia homeobox family. Studies have revealed that PBX3 plays crucial roles in tumor progression and metastasis. PBX3 upregulation has been linked to various tumors, where it contributes to cell growth and development. One of its primary functions in tumor biology is promoting cell proliferation by modulating the cell cycle. Moreover, PBX3 inhibits apoptotic pathways, allowing tumor cells to survive and resist treatment. In addition to its role in survival, PBX3 is involved in epithelial-mesenchymal transition (EMT) and enhances the invasive potential, contributing to tumor spread. It also exerts its effects through interactions with other transcription factors, including homeobox proteins, and by forming complexes that bind to specific DNA sequences, activating or repressing target gene expression. Given its central role in tumor progression, PBX3 presents a promising diagnostic and therapeutic target. The development of PBX3-specific therapies, such as proteolysis-targeting chimeras (PROTACs), could provide a novel approach for tumor treatment. While challenges remain in achieving selectivity and minimizing off-target effects, PBX3-targeted therapies have the potential to improve patient outcomes, particularly for tumors characterized by PBX3 overexpression.