A newly designed three-part molecule could be the one answer patients with a certain form of breast cancer are looking for, scientists report.
This chimera, created by a team at the Georgia Cancer Center, has the ability to simultaneously decrease the expression of three growth factors that are over-expressed in some cancers.
The growth factors are human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), and epidermal growth factor receptor (EGFR). The new chimera interferes with HER2 and HER3 signaling and ultimately leads to cancer cell death, as shown in the group's recent publication in Molecular Therapy: Nucleic Acids.
Extensive studies have found that 20% to 30% of breast cancers are characterized by over-expression of HER2, which makes the cancer cells grow and divide faster, leading to a cancer that's more aggressive and more likely to be resistant to the standard of care. Patients with this type of breast cancer tend to have a poorer prognosis.
HER family receptors EGFR, HER2, and HER3 all at once, since it is well-known that another HER family member can compensate for one that is blocked by a drug having a single target.
Each component of this tripartite molecule has potent anti-tumor activity. The molecule was designed such that the EGFR-targeting component is sandwiched between the HER2- and HER3-targeting components in what is known as a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera. This construction enables the EGFR component to reach its target within HER2- and HER3-expressing cells. Compared to individual components, the chimera is large enough to avoid renal depletion, resulting in a prolonged circulation time and increased efficiency.
The newly crafted molecule is non-toxic, simple to produce, and cost-effective compared to the production of alternate treatment strategies, such as antibodies and small molecule inhibitors.