Korea University unveils HVH-2930’s potential in HER2-positive breast cancer treatment

New Delhi: In a stride towards enhancing HER2-positive breast cancer treatment, Korean scientists at Korea University have introduced HVH-2930, an HSP90 inhibitor poised to redefine therapeutic outcomes. Unlike its predecessors, HVH-2930 bypasses the induction of the heat shock response, demonstrating compelling efficacy in inducing cancer cell apoptosis and overcoming treatment resistance. Preclinical studies have underscored its potential across diverse HER2-overexpressing malignancies, marking a pivotal advancement in cancer therapy.

HER2-positive breast cancer presents formidable challenges due to its aggressive nature fueled by HER2 protein overexpression. Current treatments typically integrate HER2-targeted therapies like trastuzumab alongside chemotherapy and hormone therapy. However, emerging resistance underscores the urgency for innovative approaches to improve patient outcomes.

Led by Professor Jae Hong Seo, the research team at Korea University achieved a significant breakthrough with HVH-2930, highlighted in their publication in Theranostics on March 31, 2024. Prof. Seo elucidates, “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 employed comprehensive in vivo and in vitro methods to investigate HVH-2930’s efficacy against HER2-positive breast cancer. Advanced cytometry techniques assessed cell viability, apoptosis, and functionality in co-cultures of breast cancer cells with normal mammary cells. Moreover, protein interaction analyses unveiled underlying molecular mechanisms, while mouse models provided insights into treatment responses and tumor dynamics.

Key findings highlight HVH-2930’s ability to induce apoptosis in breast cancer cells without triggering the heat shock response, a critical advantage over existing treatments. By selectively targeting HSP90, HVH-2930 effectively downregulates HER2 signaling, pivotal in halting breast cancer progression. In xenograft mouse models, HVH-2930 exhibited promising results by inhibiting tumor growth, angiogenesis, and cancer stem cell-like properties, all while maintaining non-toxic profiles. Additionally, its synergy with paclitaxel suggests a potent therapeutic strategy for HER2-positive breast cancer, elevating prospects for enhanced treatment protocols.

Prof. Seo emphasizes, “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 oesophagal 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.”