Scientists at the Georgia Cancer Center have created a three-part molecule that targets growth factors over-expressed in some cancers, offering a possible treatment route for patients with a certain form of breast cancer.
The chimera molecule’s targets are human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), and epidermal growth factor receptor (EGFR). The molecule interferes with HER2 and HER3 signaling and ultimately causes cancer cell death.
Previous studies have shown over-expression of HER2 to cause 20% to 30% of breast cancers. The receptor aids the rapid growth of cancerous cells, leading to a more aggressive form of the disease that is more likely to be resistant to standard-of-care treatments. Patients with this type of breast cancer often have a poorer prognosis.
The molecule is created to have potent anti-tumour activity, designed to target all three receptors simultaneously to prevent one or both compensating for the blocked action of the third.
The molecule is designed so that the EGFR-targeting component is between the HER2- and HER3-targeting components in what is known as a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera. This design allows the EGFR component to reach its target within HER2- and HER3-expressing cells.
Compared with individual components, the chimera is large enough to avoid renal depletion and allows for a prolonged circulation time and increased efficacy. It is also non-toxic, easy to produce, and cost-effective compared with the production of alternate treatment routes such as antibodies and small molecule inhibitors.
"As a bioengineer, I am developing the materials for cancer-targeted treatment," study leader Dr Hongyan Liu said.
Liu's ongoing studies test the chimera’s ability to treat breast cancers resistant to Herceptin, a drug that targets HER2.
Liu has said that the molecule could be a possible treatment route for other cancers such as lung, head and neck, as these also evidence an over-expression of the HER family.
Findings were published in Molecular Therapy: Nucleic Acids.