Andres J P Klein-Szanto

I graduated from the University of Buenos Aires Medical School in 1965 (Medico or Physician=M.D.) and after training in pathology and further postgraduate experimental pathology work that resulted in a doctorate thesis, I was awarded the Doctor in Medicine degree (1970). I worked as an Instructor and then Chief Instructor of Pathology in the Medical and Dental Schools of the University of Buenos Aires and the University of Zurich, Switzerland (1965-1977). Since 1978,  I was employed as a Senior Medical Scientist at the Oak Ridge National Laboratory and as Professor of Biology and Molecular Carcinogenesis at the M.D. Anderson Cancer Center of the University of Texas. My present position is Professor Emeritus at the Fox Chase Cancer Center, Philadelphia.
The K-S laboratory studied mechanisms of tumor progression of squamous cell carcinomas and has developed several models to evaluate the development of human cancer using xenotransplanted normal and precancerous human tissues exposed in vivo to carcinogens.  Together with my coworkers we were the first to describe in an in vivo model, the signature p53 mutations seen in tumors produced by benzo(a)pyrene, the most ubiquitous human carcinogen present in tobacco smoke. During the last two decades our work on proprotein convertases and cancer has emphasized the role of these proteases in skin squamous cancer progression as well as in several human malignancies. Partly because of these dicoveries, proprotein convertases have been recognized as targets for cancer therapy and several clinical trials are being conducted. The Klein-Szanto laboratory has published some of the first papers highlighting the role of furin in human tumor invasion and progression and has also been at the forefront of PC-inhibitor experimental treatments with CMK, PDX and PC siRNAs. The use of inhibitors helped to better understand the mechanism of PC activation of cancer-related factors such as the TGF beta, IGFR, IGFR-1, MT-MMPs, etc, but also showed the direct effect of these inhibitors on cancer cell growth and invasion in in vitro and in vivo animal models. In particular, the lab was the first to highlight the overexpression of furin in human ovarian cancer and its potential as a target for therapy (the focus of the first clinical trials). In addition, the laboratory was heavily involved in esophageal cancer research with a team at the University of Pennsylvania, later at Columbia Univ.