Targeting solid tumours with significant in vivo efficacy

siRNA, also known as short interfering RNA, is a type of non-coding double-stranded RNA of 20–23 nucleotide base pairs in length. As the name suggests, it acts by interfering with the expression of the specific gene having a complementary sequence. The siRNA binds specifically to the single gene at a particular location for gene silencing and regulation. The therapeutic potential of siRNAs has been verified in the treatment of cancer and although cancer-related RNAi drugs have not been marketed, they still have tremendous therapeutic potential.

STAT6 siRNA act to inhibit the production of STAT6 (signal transducer and activator of transcription 6) by cancer cells. STAT6 is an intracellular target which is not amenable to targeting with traditional therapeutics. STAT6 is strongly expressed in various tumours and is most highly expressed in human malignant lymphomas and pancreatic, colorectal, prostate and breast cancers. STAT6 is associated with cancer cell proliferation, an increased malignancy and poor prognosis. Thus, techniques aimed at reducing or blocking STAT6 expression may be useful in treating STAT6 high cancers.

Roquefort Therapeutic’s STAT6 siRNA family consists of multiple patented potential siRNA medicines that have demonstrated inhibition of STAT6 production and anti-cancer activity in validated in vitro and in vivo models of breast and colon cancer.

These STAT6 siRNAs demonstrated a significant reduction (P<0.01) in proliferation of both colorectal and breast with an ~50% reduction in cell growth at 7 days. This anti-cancer effect was replicated in a validated in vivo model of colorectal cancer with a significant reduction (P<0.05) in cancer weight and volume to 28 days. The clinical relevance of these findings include that silencing STAT6 could lead to better prognosis in later stages of cancer and may reduce the need for chemotherapy, and thus the side effects linked to it, while still reducing cancer size and killing the cells.