Abstract

Early drug discovery for cancer treatment was based on targeting known proliferation mechanisms and the disruption of essential cellular functions. These therapies, although specific, were shown to have a wide range of toxicities. In contrast, therapies targeted to non essential functions were less toxic and less effective. Currently, the discovery phase has shifted to identify targeted therapies without specific molecular targets in mind. This approach allows for the identification of compounds against multiple targets or cancer pathway specific molecules. Furthermore, the identification of compounds that are efficacious and safe, particularly at the level of the immune system, will result in overall better therapies being developed. In this proposal various genomic and proteomic tools will be used to advance the identification of novel therapeutic compounds. A 150,000 molecule chemical library has been pre‐screened at various levels and narrowed down to 8 lead compounds. These compounds have minimal toxic effects on the immune system and will be further evaluated to identify the genomic and proteomic signatures for safety, efficacy and dose. We will also elucidate the molecular pathways that are targeted as they relate to cancer. This research is supported by funding to JX She.

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