Overview 

The potential therapeutic effects of Honey Bee Venom and Melittin in treating aggressive TNBC and HER2-Enriched Breast Cancer presented up to this point show some incredible promise for early stage investigations of a novel Breast Cancer treatment. Going forward, researchers will surely focus on optimizing the delivery method of Melittin and Bee Venom treatments to enhance the treatment specificity for cancer cells and limit collateral damage to healthy tissues. Furthermore, the potent and rapid effects that Honey Bee Venom and Melittin imposed on the Receptor Tyrosine Kinase pathways implicates a potential role for Honey Bee Venom in the treatment of other cancer types that overexpress these receptors.

The Future of Melittin Delivery

Although several experiments in this chapter demonstrated the specificity of Melittin’s toxic effects for Breast Cancer cell lines, past studies have well characterized the hemolytic activity of Honey Bee Venom and Melittin on Red Blood Cells (Watala and Kowalczyk, 1990). Therefore, intravenous delivery methods for a potential Melittin cancer therapy to minimize off-target effects has been an area of particular interest. Nanocarriers such as liposomes, polymers, or carbon-based material have been employed in several different forms as a delivery mechanism to release Melittin directly at the tumor-site, avoiding its cytotoxic effects on healthy cells along the way. These Nanopeptides, dubbed “Nanobees”, generally employ highly specific receptor-targeted binding motifs to release cytotoxic Melittin at the site of the cancer with high precision (Pan et al. 2011). Follow-up studies that investigate treatment options for aggressive breast cancers with Melittin may focus on employing different types of Nanoparticles to optimize the delivery of Melittin to the breast cancer site, while minimizing its off-target effects on healthy cells.

Different classes of Nanocarrier vehicles. Several Nanobee molecules have employed the use of Liposome class Nanocarriers for Melittin delivery (Pan et al., 2011).

Soman et al. (2009) produced a Perfluorocarbon based Nanoparticle packaged with Melittin that was capable of delivering a large portion of Melittin directly to Murine tumor sites in vivo without imposing any significant toxicity on their mice models. This is an additional Nanocarrier class that may warrant further research in the targeted delivery of Melittin to Breast Cancer sites.

Perfluorocarbon nanoparticles are highly stable molecules capable of packaging pharmaceutical agents for delivery (Chen et al. 2013).

Expanding the Scope: Breast Cancer and Beyond

Melittin and Honey Bee Venom were able to rapidly shut down the HER2 and EGFR Receptor Tyrosine Kinase Pathways in HER-2 Enriched and TNBC cell lines, respectively. It has long been understood that these two RTK pathways are principal oncogenes underlying dysregulated cell proliferation and differentiation in breast cancer subtypes, as well as a range of additional cancer groups (Hsu and Hung, 2018). EGFR mutations are seen frequently in glioblastoma and colorectal cancers, while HER2 overexpression encompasses ovarian, gastric, and esophageal cancer subtypes. Given the potent effects observed on suppression of RTK phosphorylation in breast cancer cell lines, future studies will almost certainly investigate if these anticancer effects are extended to other HER2 and EGFR overexpressing cancer lines as well.

A non-exhaustive list of cancer types that have been known to overexpress the EGFR and HER2 Receptor Tyrosine Kinases. © BioRender.

References