Electroporation Therapy with Bleomycin (EPT-B) holds promise for the treatment of primary and secondary liver cancer. By applying brief electrical pulses to tissue, transient increases in cell membrane permeability can be induced. As a result, cellular uptake of membrane limited substances, such as bleomycin, is greatly potentiated. Therapeutic benefit is then derived from the action of the loaded agent. While the therapeutic effects of EPT-B have already been demonstrated, the potential toxicities associated with the procedure are not fully characterized, especially in liver tissue. Research proposed for SBIR phase includes in vitro confirmation of proposed drug dosages followed by large animal toxicology studies designed to identify adverse effects associated with EPT- B. Since the preservation of functional liver parenchyma is critical to patient survival, it is imperative to understand the effects of the therapy in both normal and cirrhotic liver tissue prior to the initiation of human studies. Testing of cirrhotic tissue has particular significance for primary liver cancer patients, since they often present with underlying liver disease. Upon successful completion of the toxicology studies and submission of an IND amendment, Ichor proposes to conduct a clinical investigation of EPT- B for primary liver cancer under SBIR Phase II.
Electroporation Therapy has potential as a loco-regional treatment for both primary and secondary liver tumors. Preclinical work in small animals indicates that EPT has significant therapeutic effect in a wide range of tumor types, including hepatocellular carcinoma. After the proposed toxicology studies have been completed, the initial focus will be on the treatment of local, unresectable primary liver cancers for which no suitable treatment alternative exists. These patients make up a significant portion of the primary liver cancer patients in the US. Future investigations of EPT in liver tissue will also include the delivery of gene based therapies.
