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Page 21 of 36 J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21

26. Human-enzyme mediated, systemic depletion of amino acids for cancer prevention and
treatment

John DiGiovanni

Division of Pharmacology & Toxicology, College of Pharmacy and Live STRONG Cancer Institutes, Dell
Medical School, the University of Texas at Austin, Austin, TX 78712, USA.

Significant differences exist between the metabolism of normal and malignant cells. We have recently
evaluated two potential therapeutic enzymes that degrade critical amino acids required for tumor
growth. These engineered human enzymes, one that degrades cystine/cysteine [Cyst(e)inase] and one
that degrades methionine (Methioninase), are currently under investigation for anticancer activity with
promising preclinical results for prostate cancer as well as several other cancers. Depletion of extracellular
cystine/cysteine leads to depletion of intracellular cysteine, decreased levels of intracellular glutathione
(GSH) and increases in intracellular ROS leading to activation of cellular signaling pathways and cancer
cell death. Depletion of extracellular methionine leads to reductions in intracellular L-methionine,
S-adenosylmethionine and polyamines as well as reduced levels of cysteine and GSH and cancer cell
death. Both enzymes given i.p. significantly reduced serum levels of their respective amino acid targets and
significantly inhibited tumor growth in vivo. These and other studies on the mechanisms associated with
their potential anticancer activity will be presented. In addition, studies are underway to identify agents
that would synergize with one or both of these enzymes for enhanced therapeutic efficacy. Promising
results have been obtained through targeting parallel antioxidant defense pathways and mitochondrial
metabolism and these results will also be presented. Research supported by NIH NCI grant CA189623.

Biography
John DiGiovanni received his BS degree in Pharmacy and his PhD degree in Pharmacology from the
University of Washington, Seattle, Washington. He did his postdoctoral work at the McArdle Laboratory
for Cancer Research, University of Wisconsin, Madison, WI in carcinogenesis and cancer biology. Dr.
DiGiovani joined the University of Texas at Austin (UT Austin) in January of 2010 and is Professor in the
Division of Pharmacology and Toxicology, College of Pharmacy. He holds the Coulter R. Sublett Endowed
Chair in Pharmacy. He also has adjunct appointments in the Department of Nutritional Sciences (College
of Natural Sciences) and the Department of Pediatrics (Dell Medical School). In addition, Dr. DiGiovanni
is Director of the Center for Molecular Carcinogenesis and Toxicology (CMCT) at UT Austin and is
Associate Director for Basic Research in the LiveSTRONG Cancer Institutes, Dell Medical School at UT
Austin. He is the Editor-in-Chief for the journal Molecular Carcinogenesis. Dr. DiGiovanni has published
more than 250 research articles in prestigious peer-reviewed journals and more than 50 invited reviews/
book chapters.

27. Cancer stem cells and miRNA in osteosarcoma

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Gaia Palmini , Cecilia Romagnoli , Roberto Zonefrati , Gianna Galli , Francesca Marini , Alessandra
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Aldinucci , Carmelo Mavilia , Gigliola Leoncini , Antonella Simoni , Alessandro Franchi , Giovanni
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Beltrami , Domenico Andrea Campanacci , Rodolfo Capanna , Maria Luisa Brandi 1
1 Dipartimento di Chirurgia e Medicina Traslazionale, Università degli Studi di Firenze, Firenze 50121, Italy.
2 Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di
Firenze, Firenze 50121, Italy.