Abstract 5484: Simultaneous targeting of EGFR and MET pathways using nanotechnology improves the treatment outcomes of photodynamic therapy for pancreatic cancer

Abstract

Abstract Pancreatic Cancer (PanCa) is difficult to treat due to its inherent resistance to most therapies. First line chemotherapy only has a 5% response rate that yields a dismal prognosis of 6-month median survival and <4% 5-year survival. Combination therapies only showed modest benefits and there are still vital unmet needs for alternative treatment that improve overall patient survival. Photodynamic Therapy (PDT), a light-regulated cytotoxic therapy, showed promise as a new treatment modality for PanCa which improved median survival from 6 to 9.5 months in a pilot clinical trial. This result triggered our preclinical development of PDT combination regimen targeting proliferative pathways to further enhance treatment outcome. Using nanotechnology, we designed and synthesized nano-constructs co-encapsulating multiple therapeutic agents that can simultaneously target EGFR and MET-regulated proliferative pathways in combination with cytotoxic PDT treatment. We tested these nano-constructs in orthotopic pancreatic cancer models for treatment efficacy and our major findings include: 1) The nanoscale multidrug delivery system allows simultaneous targeting of EGFR and MET-regulated proliferative pathways and offered the best reduction of local tumor burden and metastatic burden to lymph nodes, lung and liver. With only one time of treatment, the local tumor burden is reduced to 10% of that of non-treated, and significant reductions of organ metastasis were also achieved. 2) The nanoscale multidrug delivery system delivers PDT agent and MET inhibitor PHA-665752 with higher payload and reduces their systemic toxicity. The EGFR inhibitor Cetuximab is delivered intracellularly into cancer cells, which targets both intracellular and cell surface EGFR. Intracellular delivery of Cetuximab increased treatment efficacy compared to naked Cetuximab. We are continuing optimizing the scheduling of individual treatments to further improve treatment outcomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5484.