Targeted Therapy for Triple-Negative Breast Cancer

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.