Bio-Synthesis, Inc. to supply peptide-BNA for the treatment of triple negative breast cancer
Cancer continues to pose a problem as approximately ~1500 are expected to die daily from cancer in the U.S. alone. Breast cancer is the leading type of cancer for women and is more common with higher survival rates in developed world. In addition to conventional therapies, treatments include hormone blocking therapy and targeted therapy, ex. trastuzumab inhibiting human epidermal growth factor receptor 2 (Her2) receptor. (Alvarez et al., 2010).
For therapy, breast cancers are often classified according to their ‘triple status’. Triple status refers to the expression level of human epidermal growth factor receptor 2 receptor (Her2), estrogen receptor (ER), and progesterone receptor (PR). Triple negative breast cancer lacks the expression of these receptors, undermining the efficacy of drugs targeting these receptors. Given their poor survivability, an urgent need exists to develop novel therapies.
Oncogenic signaling pathways driven by protein kinase B (AKT) or mitogen activated protein kinase (MAPK) play a critical role in regulating the growth of various human cancers including breast cancer (Samadi et al. 2018). The activity of these kinases is negatively regulated by phosphatases.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting mRNAs for degradation or suppressing mRNA translation. The microRNA miR-21 was shown to be upregulated in human breast cancer cells (Iorio et al., 2005). As the targets of miR-21 include tumor suppressors phosphatase and tensin homolog (PTEN) (Meng et al., 2007) and human MutS protein homolog 2 (hMSH2) (Valeri et al, 2010), suppressing the activity of miR-21 represents an attractive approach for treating triple negative breast cancer.
A promising therapy is to devise an oligonucleotide-based blocking agent that hybridizes to miR-21 in the RNA-induced silencing complex (RISC) to free target mRNAs from degradation. The potency of the miR-21 blocker could be greatly improved by using aminomethyl bridged nucleic acid (BNA) as it allows better base-pair stacking and a high stability, elevates Tm, and lowers toxicity (Rahman et al 2007). Thus, the therapeutic efficacy of the miR-21 blocker could be increased through the BNA technology.
Bio-Synthesis, Inc. is uniquely poised to provide BNA as it has acquired a license from BNA Inc. of Osaka, Japan for the manufacturing and distribution of BNA-NC, a third generation of BNA oligonucleotides. Recently, Bio-Synthesis, Inc. has entered into collaborative agreement with Bound Therapeutics LLC. to synthesize miR-21 blocker using BNA. To provide tumor selectivity, the miR-21 blocker will be conjugated to a peptide that allows selective uptake by breast cancer cells.
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