Breast cancer is the second leading cause of death in women and is the most common cancer among women worldwide. There are four main breast cancer subtypes, luminal A, luminal B, HER2-positive and triple-negative. Triple-negative breast cancer (TNBC) is highly invasive and has higher rates of metastasis and a worse prognosis. Metastasis of cancer cells is the primary cause for most cancer-related deaths, and as such, metastatic steps are potential targets for cancer treatment. HER1 and HER3 receptors are overexpressed in most TNBCs and inappropriate activation of these receptors is associated with metastasis and therapeutic resistance. While there are several antibody and antibody-conjugate agents targeting HER1 and HER3 receptors, chemotherapeutics are still the main systemic treatment for TNBC and they show limited efficacy with high toxicity in patients.
Researchers at the Biodesign Institute of Arizona State University in collaboration with researchers at Cedars-Sinai have developed novel nanoparticle-based targeted therapeutics for TNBC cells. These therapeutics tightly bind HER1+ and/or HER3+ TNBC cells at the cancer site as well as in circulation, preventing metastasis in its initial stage. The nanoparticles also have small molecule anticancer payloads reversibly bound to them, which are released when the TNBC cells are crosslinked. The therapeutics have a drug-to-cargo ratio of 50, with slow release over time, resulting in efficient death of crosslinked TNBC cells.
These novel therapeutics specifically target HER1- and/or HER3-overexpressing TNBC cells block invasion and metastasis as well as kill the cells with a substantial anticancer payload and represent a potential breakthrough in the treatment of TNBC patients.
Potential Applications
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Targeted TNBC therapeutics
Benefits and Advantages
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The molecules that bind HER1 and HER3 can be expressed at high levels in DE3 cells and are more cost efficient to produce than monoclonal antibodies
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Have similar high affinities to their HER receptors as monoclonal antibodies
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96% crosslinking efficiency
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99% migration inhibition
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90% invasion inhibition
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Binds to many copies of small molecule therapeutics
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Slowly released for prolonged effects
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Drug-to-cargo ratio of 50
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Crosslinking the TNBC cells blocks undesired dissociation of cells from the primary tumor
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May also be able to bind to circulating tumor cells to prevent seeding of metastatic cells in distant tissue
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For cells that have already escaped the primary tumor, this could block the development of a secondary tumor
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For more information about the inventor(s) and their research, please see