Pinku Mukherjee
University of North Carolina at Charlotte and Oncotab Inc.
Title: Development of Targeted Therapies for Pancreatic Cancer
Biography
Biography: Pinku Mukherjee
Abstract
The study explores a novel strategy to deliver drugs to pancreatic ductal adenocarcinoma (PDA) to combat a) chemo-resistance and b) toxicity associated with systemic delivery of chemotherapeutic drugs. We also report the development of an accurate diagnostic/imaging test for PDA. Globally, this year, it is estimated that ~350,000 patients will die of PDA. Development of a biomarker for accurate diagnosis and targeted therapy to improve patient outcome are of paramount importance. Emerging evidence suggests that the capability of a tumor to propagate is dependent on a small subset of cells within the tumor, termed cancer stem cells (CSCs). Traditional treatments can miss the CSCs due to its quiescent property. We have developed a novel monoclonal antibody (designated TAB004) that recognizes a previously hidden cancer biomarker tMUC1 (tumor-specific MUC1). We have reported that tMUC1 is expressed on 95% of PDA and on all PDA-associated CSCs. In this study, we have covalently bound TAB004 to various drug-loaded PLGA (Poly lactic-co-glycolic acid) and silica-based nanoparticles (NPs). These formulations specifically target the tMUC1 on PDA, and associated CSCs sparing normal tissue. We hypothesize that NPs bound to TAB004 will enable the use of highly cytotoxic anti-cancer treatments at localized concentrations making the treatment more effective at lower doses, increasing its therapeutic index and limit toxicity. We will present the results on the localization and therapeutic efficacy of such formulations in appropriate mouse models. Further, we will report on the diagnostic/imaging application of TAB004 to monitor response to therapy.