Non-Melanoma Skin Cancer (NMSC)
Non-Melanoma Skin Cancer (NMSC) originates in the basal cells or squamous cells of the epidermal layer of the skin. Basal Cell Carcinoma (BCC) accounts for 75-80% of all skin cancers while squamous cell carcinoma (SCC) accounts for ~20%. TGF-β1 has been identified as a major factor that promotes epithelial cell proliferation and is a critical regulator of NMSC development and progression in humans. COX-2 is also required by the myeloid suppressor cells to produce an immunosuppressive molecule (arginase-1) that promotes the invasion and angiogenesis of human NMSC cells. STP705 is delivered intradermally to the tumor site resulting in localized silencing of TGF-b1 and Cox-2, killing of the tumor cells and a reduction in tumor size.
Cholangiocarcinoma (CCA) is a cancer that can form in the bile ducts of the liver. It is a rare disease but while it typically occurs in patients over 50 years old it can occur at any age. The tumor is very difficult to treat. It is often caused by inflammation and many PSC patients will eventually develop CCA. Age (>50) and smoking are significant additional risk factors for the disease.
HCC is a cancer within the liver. It is most often caused by liver damage induced by Cirrhosis caused by infections from viruses such as Hepatitis B and Hepatitis C. Treatment options currently involve surgery, liver transplantation, chemotherapy and/or or radiation treatment. Sorafenib (Nexavar; a kinase inhibitor) may slow disease progression in advanced cases but there is a need for efficacious therapeutics that produce a cure.
In patients with liver cancer who fail to show improvement when treated with Sorafenib the USFDA has approved treatment with the mAb therapeutic Opdivo (Nivolumab; a PD-1 checkpoint inhibitor). Sirnaomics is working to develop siRNA therapeutics that augment the action of the immune checkpoint inhibitors to improve the clinical outcomes for patients with liver cancer (HCC).
Sirnaomics has active programs to identify siRNAs that can silence key driver genes of importance in tumors such as Pancreatic and other cancers. Sirnaomics also has active programs to find siRNAs that can augment the activity of approved therapeutics in these indications. PNP can deliver 2 siRNAs to the same cells within the same tissues and so we can target multiple pathways within the cancer cells – preventing them from escaping therapeutic pressure by expressing genes in a resistance mechanism.
PSC or Primary Sclerosing Cholangitis
PSC is a disease affecting the bile ducts of the liver. In this disease inflammation progressively produces scarring within the bile ducts. The disease progresses slowly but the scarring can result in tumors within the liver or bile ducts and can lead to liver failure. The only cure is a liver transplant but PSC can sometimes reoccur within the transplanted liver.