Potential of Theranostic Target Mining in the Development of Novel Diagnostic and Therapeutic Products in Oncology: Progranulin/GP88 as a Therapeutic and Diagnostic Target for Breast and Lung Cancers.

Abstract

Biological therapy with companion diagnostic such as the combination of anti-Her-2 therapy (Herceptin™) and measurement of Her-2 expression in breast tumors (HercepTest™) has proven successful in Oncology. Screening targets that have both diagnostic and therapeutic applications (theranostic targets) at the discovery stage should provide the best strategy for the development of novel targeted therapies with companion diag- nostics in Oncology. This strategy is at the basis of the product pipeline developed by A&G Pharmaceutical. To identify theranostic targets, A&G has developed a biological screen for functional drivers of tumorigenesis abnormally expressed in cancer tissues when compared to normal tissue counterparts. The advantage of this strategy is that identified targets will combine from the start, diagnostic and therapeutic applications. A&G has identified a secreted 88 kDa autocrine growth and survival factor, GP88 (progranulin) overex- pressed in cancer tissue and has demonstrated its critical role in the biological process of breast cancer devel- opment, invasiveness, survival and drug resistance. A protein/antibody-based pipeline consisting of prod- ucts able to detect GP88 in tissues, in circulation and to block GP88 was developed at A&G. This pipeline combines a neutralizing anti-GP88 monoclonal antibody therapeutic with two companion diagnostic tissue (IHC) and serum (EIA) tests. Diagnostic kits for measurement of GP88 in tissue and serum of cancer pa- tients have been validated in clinical studies. Preclinical and pathological studies support the importance of diagnostic and therapeutic products and the potential of GP88 targeted therapy with companion diagnostic in the clinical settings for several cancer indications such as anti-estrogen resistant breast cancer. [Review].