Abstract P5-08-08: A human epidermal growth factor receptor 3 (HER3)-binding nanoparticle targets and kills Herceptin®-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer

摘要: The human epidermal growth factor receptor subunit (HER2), or ErbB2, is a tyrosine kinase that amplified in approximately 20-25% of invasive breast cancers. Anti-HER2 therapies such as trastuzumab (Herceptin®) have become important the management aggressive and metastatic cancer. Although many patients with HER2-positive cancer initially respond to anti-HER2 treatments, Herceptin, significant portion them develop resistance these therapies. Consequently, there great need will treat tumors once they resistant. Recently it has been shown another member HER family, HER3, commonly upregulated tumors. This led us unique drug delivery protein (HerPBK10) specifically targets cell surface receptor, HER3. HerPBK10, bound HER3 triggers rapid endocytosis endosomal penetration, enabling deliver toxic payload cell, resulting death. We hypothesized cytotoxic drugs delivered by HerPBK10 would induce targeted death Herceptin-resistant, HER2+ cancers provide an effective treatment for whose resistant traditional demonstrated binds three different lines this binding can be competitively inhibited free ligand, indicating Next, we showed multiple Herceptin-resistant levels are significantly increased drug-resistant cells, confirming results other researchers. then assembled our molecule, chemotherapeutic doxorubicin. nanoparticle, called HerDox, was used two susceptible Herceptin had acquired resistance. HerDox caused all lines, but at greater level lower dosage lines. also compared effect nanoparticle overall In addition, combined together, induced even These indicate targeting efficiently kills cells potential either single part combinatorial therapy eliminating process verifying findings vivo order demonstrate who non-responsive Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-08.