DescriptionOne of the most pressing health concerns in recent history is cancer. The World Health Organization reports that more than 10 million cases of cancer are diagnosed each year [1]. In the United States, it is the second leading cause of death and is responsible for approximately one in four deaths in the general population [2]. Currently, only about 25% of patients treated with a certain treatment will show a response in the clinic [3]. Therefore, it is necessary to design methods for improvement patient outcomes once being diagnosed with the disease. Precision medicine is a newly found trend in the field of pharmacology to treat patients with more specified treatment regiments for increased efficacy. Patients are further categorized into subtypes based on histology of the disease and new methods are being investigated to further stratify patients based on molecular biology and on the genetic level of the disease in individual patients.
The purpose of the current proposal is to help design precision treatment of ovarian cancer patients. First, we obtained patient biopsy samples from the Cancer Institute of New Jersey and constructed gene expression profiles to help identify key dysregularities in patients and design an efficient way to screen further patients for these biomarkers. Once gene expression profiles were obtained, we targeted certain overexpressed genes through RNA interference (RNAi) therapy to downregulate their expression in the cancer cells. RNAi therapy was combined with traditional small molecule chemotherapeutics to improve their efficacy compared to being used alone to treat the patients. We categorized and optimized liposomal and dendrimer drug delivery systems (DDSs) to help delivery our proposed combinational therapies. Several small molecule chemotherapeutics were formulated separately with RNAi therapy and evaluated against monotherapies of the corresponding drug. We successfully demonstrated these DDSs efficiently delivered our combinational therapies to tumors, reduced off-site accumulation of the therapeutics, and raised the efficacy of the treatment compared to monotherapies of the corresponding drug.