Korea University identifies novel inhibitor HVH-2930 showing promise in overcoming trastuzumab resistance in HER2-positive breast cancer

HER2-positive breast cancer, known for its aggressive nature due to the overexpression of the HER2 protein, poses significant challenges in treatment. Current standard treatments for HER2-positive breast cancer typically involve a combination of HER2-targeted therapies like trastuzumab, chemotherapy, and hormone therapy. However, the emergence of resistance highlights the need for novel approaches for improved outcomes.

In this relentless pursuit of treatment solutions, a team of researchers at Korea University led by Professor Jae Hong Seo have achieved a significant milestone with the development of HVH-2930, a promising inhibitor targeting heat shock protein 90 (HSP90), the findings of which were published in Theranostics on 31 March 2024. Prof. Seo shares, “We have highlighted the pivotal role of HSP90, an oncogenic protein, in fueling tumor growth by activating key receptor tyrosine kinases, including HER2. While previous N-terminal HSP90 inhibitors faced challenges like inducing the heat shock response (HSR) and toxicity, HVH-2930, a C-terminal HSP90 inhibitor, shows promise.”

The study utilized both in vivo and in vitro methods to investigate HER2-positive breast cancer and potential treatments. In laboratory settings, breast cancer cells were cultured alongside normal mammary cells, using advanced cytometry techniques to assess cell viability, apoptosis, and functionality. Additionally, protein interactions were studied to uncover underlying molecular processes. In mouse models, tumor cell implantation was used to study tumor growth dynamics and treatment responses.

The findings revealed that HVH-2930 effectively induced apoptosis in breast cancer cells without triggering the heat shock response (HSR), a notable feature that distinguishes it from other treatments. By selectively targeting HSP90, HVH-2930 downregulated HER2 signaling, crucial in breast cancer progression. Impressively, in xenograft mouse models, HVH-2930 inhibited tumor growth, angiogenesis, and cancer stem cell-like properties without causing toxicity. Moreover, when combined with paclitaxel, HVH-2930 exhibited a synergistic antitumor effect, suggesting its potential as a promising therapeutic strategy for HER2-positive breast cancer.  These results signify a significant advancement in targeting the HSP90 chaperone machinery for breast cancer treatment.

Prof. Seo shares “HVH-2930 stands as a groundbreaking advancement in meeting the critical needs of HER2-positive breast cancer patients, notably those resistant to trastuzumab. With its potential application in other HER2-overexpressing cancers like gastric and esophageal cancers, it holds promise for treating a wider range of patients. Moreover, its anticipated affordability compared to current therapies could significantly enhance accessibility, particularly in resource-limited settings such as underdeveloped countries.”

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Reference                                    

Title of original paper: The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer

Journal: Theranostics

DOI: https://doi.org/10.7150/thno.93236

About Korea University College of Medicine

Korea University College of Medicine is the medical school of Korea University. It is located in Seoul, South Korea. As one of the oldest medical schools in South Korea, it has been historically regarded as one of the country's top medical schools. The school was founded as Chosun Women's Medical Training Institute in 1928 by Rosetta Sherwood Hall. The institute was subsequently renamed several times and ultimately merged with Korea University to become Korea University College of Medicine. So far, the school has produced over 7,000 graduates, most of whom are working as prominent physicians and public health advocates worldwide.

Website: https://medicine.korea.ac.kr/en/index.do

About the author

Jae Hong Seo, Professor at Korea University School of Medicine and Director of the Korea University Cancer Institute, has extensive experience in cancer research. He earned his doctoral degree from Korea University School of Medicine and completed postdoctoral research at the University of Massachusetts, USA. With over 130 publications and 37 patents, his focus lies in anti-cancer treatments and new drug development. Currently, Prof. Seo's team is dedicated to overcoming resistance and metastasis in HER2-positive and triple-negative breast cancers. Their efforts aim to bring hope to patients through targeted treatments.