Minsu Park, Eunsun Jung, Jung Min Park, Soeun Park, Dongmi Ko, Juyeon Seo, Seongjae Kim, Kee Dal Nam, Yong Koo Kang, Lee Farrand, Van-Hai Hoang, Cong-Truong Nguyen, Minh Thanh La, Gibeom Nam, Hyun-Ju Park, Jihyae Ann, Jeewoo Lee, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo
Rationale: Resistance to targeted therapies like trastuzumab remains a critical challenge for HER2-positive breast cancer patients. Despite the progress of several N-terminal HSP90 inhibitors in clinical trials, none have achieved approval for clinical use, primarily due to issues such as induction of the heat shock response (HSR), off-target effects, and unfavorable toxicity profiles. We sought to examine the effects of HVH-2930, a novel C-terminal HSP90 inhibitor, in overcoming trastuzumab resistance. Methods: The effect of HVH-2930 on trastuzumab-sensitive and -resistant cell lines in vitro was evaluated in terms of cell viability, expression of HSP90 client proteins, and impact on cancer stem cells...
2024: Theranostics