Research ArticleBreast Cancer

Targeted Delivery of PLK1-siRNA by ScFv Suppresses Her2+ Breast Cancer Growth and Metastasis

Science Translational Medicine  18 Apr 2012:
Vol. 4, Issue 130, pp. 130ra48
DOI: 10.1126/scitranslmed.3003601

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A Bull’s-Eye for Breast Cancer

The goal in archery is to hit the center of the target. Although this could be accomplished by randomly shooting a barrage of arrows, it would be more efficient—and less likely to provoke emergency room visits—to aim straight at the bull’s-eye. Cancer therapies work on a similar principle. Broad therapies may treat the cancer but have many unwanted effects on healthy tissue. Yao et al. now target cancer drugs directly to the tumor using single-chain fragmented antibodies (ScFvs).

About 60% of metastatic breast cancers that express human epidermal growth factor receptor 2 (Her2) do not respond to the anti-Her2 therapeutic antibody trastuzumab. The authors hypothesized that ScFvs specific to Her2 could deliver small interfering RNA (siRNA) to Her2+ breast cancer cells. They complexed siRNA for Polo-like kinase 1 (PLK1), which promotes cell division, with a Her2-ScFv-protamine peptide fusion protein (F5-P). This complex suppressed Her2+ breast cancer cell lines and primary human cancers in orthotopic breast cancer models. The siRNA complexes slowed tumor cell growth, reduced metastasis, and prolonged survival with no observed toxicity. The antitumor effects were even greater when a mix of siRNAs was delivered. These results suggest that as a new platform to deliver siRNAs to specifically treat Her2+ breast cancers, F5-P may be on target.