Glioblastoma multiforme (GBM) is the deadliest form of brain tumor, and effective treatments are lacking. Thus, a new generation of effective treatments is urgently needed. B-cell lymphoma 6 (BCL6) is a transcription factor that functions to suppress the transcription of DNA damage response genes, halting cell death in response to DNA damage. Here, we identified BCL6 as a lynchpin in GBM, the expression of which was greater in GBM cells than in normal cells and associated with poor survival in GBM patients. The silencing of BCL6 additionally affected GBM cell proliferation and triggered cellular damage. Furthermore, we reported the identification of YK01, a novel small-molecule inhibitor of BCL6. YK01 exhibited excellent anti-GBM bioactivity and caused apoptosis; importantly, YK01 significantly inhibited the growth of GBM cells both in vitro and in vivo. Moreover, the combination of YK01 and temozolomide treatment significantly suppressed the growth and metastasis of tumors in vivo and prolonged the survival of mice with tumors. In summary, our findings reveal that BCL6 appears to play a crucial role in GBM and may be a therapeutic target for treating this incurable condition.

Gastric cancer is highly prevalent among digestive tract tumors. Due to the intricate nature of the gastric cancer immune microenvironment, there is currently no effective treatment available for advanced gastric cancer. However, there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4 (EP4) in gastric cancer. In our previous study, we identified a novel small molecule EP4 receptor antagonist called YY001. Treatment with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse model. Furthermore, administration of YY001 stimulated a robust immune response within the tumor microenvironment, characterized by increased infiltration of antigen-presenting cells, T cells, and M1 macrophages. Additionally, our research revealed that YY001 exhibited remarkable synergistic effects when combined with the PD-1 antibody and the clinically targeted drug apatinib, rather than fluorouracil. These findings suggest that YY001 holds great promise as a potential therapeutic strategy for gastric cancer, whether used as a standalone treatment or in combination with other drugs.