Targeted approaches for HER2 breast cancer therapy: News from nanomedicine?

Abstract

About 30% of human breast cancers are human epidermal growth factor receptor 2 (HER2)⁺. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2⁺ cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clinical outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the development of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional compartimentalization, which allows to combine the specific target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photothermal ablation or in photodynamic therapy have been functionalized in order to match specificity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2⁺ breast cancer and anti-HER2 therapy, in particular deepening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted nanoparticles for HER2⁺ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical practice; however promising results encourage an upcoming translation of this research for the next future.

Keywords: Human epidermal growth factor receptor 2, Human epidermal growth factor receptor 2⁺-breast cancer, Nanomedicine, Nanoparticle, Targeted-therapy

Core tip: About 30% of human breast cancers are characterized by the overexpression of human epidermal growth factor receptor 2 (HER2) receptor, which determines the deregulation of cell survival and proliferation pathways. The HER2-targeted therapy is the most effective treatment, despite some related limitations, which could be bypassed with the development of nanoparticles for HER2-targeted drug delivery, photothermal ablation or photodynamic therapy. Here, we describe HER2⁺ breast cancer features and anti-HER2 therapy, and focus on the contribution of nanomedicine in this context, by reporting HER2-targeted nanoparticles under preclinical investigations. Promising results suggest upcoming clinical application of these nano-compounds in the next future.