New C-terminal HSP90 Inhibitor Demonstrates Efficacy Against
Drug-Resistant Breast Cancer Cells
SEOUL,
South Korea, June 26,
2024 /PRNewswire/ -- Korean scientists have
investigated HVH-2930, an innovative HSP90 inhibitor in reshaping
HER2-positive breast cancer treatment. Unlike previous HSP90
inhibitors, this compound circumvents limitations by bypassing heat
shock response induction. It demonstrates promising efficacy in
inducing cancer cell apoptosis and effectively overcomes treatment
resistance. In preclinical studies, HVH-2930 showed substantial
promise, offering hope for better treatment outcomes. Its potential
for diverse HER2-overexpressing malignancies indicates a paradigm
shift in cancer therapy, anticipating enhanced effectiveness and
increased availability.
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."
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
Website:
https://medicine.korea.ac.kr/en/index.do
Media Contact:
Soo-Jin
Jeon
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SOURCE Korea University College of Medicine