Targeting HSP70-E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer.

Cervical cancer is predominantly driven by persistent infections with high-risk human papillomavirus and the continuous activity of its E6 and E7 oncoproteins. This study explored the role of heat shock proteins 70 kDa (HSP70s) in enhancing the function of these oncoproteins and examined the impact of SHetA2, an investigational new drug, on this interaction. We found that HSP70 specifically binds to E7, but not E6, protein and that SHetA2 disrupts this binding. This disruption led to a significant reduction in E6 and E7 mRNA and E7 protein levels, while effects on E6 protein levels were minimal. SHetA2 treatment also resulted in altered levels of cell cycle regulatory proteins, reduced cell cycle progression, and decreased metabolic viability in cervical cancer cell lines and xenograft models. These findings support the potential of SHetA2 to impair cervical cancer progression by targeting HSP70/E7 interactions, highlighting its promise as a therapeutic strategy for treating cervical cancer.