Targeting Transcription Factor YY1 for Cancer Treatment: Current Strategies and Future Directions

SIMPLE SUMMARY: Cancer is a global health problem with severe consequences. Certain genes, known as transcription factors (TFs), are overactive in many tumors. Targeting these TFs could be an effective approach to combat cancer. One such TF is called yin yang 1 (YY1) and plays important roles in tumor development. In preclinical studies, inhibiting YY1 has shown promise in slowing tumor growth, promoting cell death, and increasing the effectiveness of chemotherapy. Recent research suggests that combining YY1 inhibition with immunotherapy may enhance the effectiveness of treatment. However, there are challenges in developing drugs that specifically target YY1 and delivering them into the tumor. This review explores YY1 biology, its role in cancer, and various strategies for targeting YY1, including small molecule inhibitors, RNA interference, and gene editing techniques. The findings highlight the clinical implications of YY1-targeted therapy and the potential for novel therapeutic approaches that can improve patient outcomes. ABSTRACT: Cancer represents a significant and persistent global health burden, with its impact underscored by its prevalence and devastating consequences. Whereas numerous oncogenes could contribute to cancer development, a group of transcription factors (TFs) are overactive in the majority of tumors. Targeting these TFs may also combat the downstream oncogenes activated by the TFs, making them attractive potential targets for effective antitumor therapeutic strategy. One such TF is yin yang 1 (YY1), which plays crucial roles in the development and progression of various tumors. In preclinical studies, YY1 inhibition has shown efficacy in inhibiting tumor growth, promoting apoptosis, and sensitizing tumor cells to chemotherapy. Recent studies have also revealed the potential of combining YY1 inhibition with immunotherapy for enhanced antitumor effects. However, clinical translation of YY1-targeted therapy still faces challenges in drug specificity and delivery. This review provides an overview of YY1 biology, its role in tumor development and progression, as well as the strategies explored for YY1-targeted therapy, with a focus on their clinical implications, including those using small molecule inhibitors, RNA interference, and gene editing techniques. Finally, we discuss the challenges and current limitations of targeting YY1 and the need for further research in this area.