Table 2.

Strategies for reducing cancer progression by targeting l-arginine metabolism

Strategies
A. Increasing T cell anti-tumor immune function by decreasing myeloid derived suppressor cells (MDSC) number or activity
1) DFMO: reduces the number of MDSC, inhibits ODC and arginase activity, and decreases polyamine formation (93, 136, 141, 241)
2) Arginase inhibitors: increase l-arginine and reduce l-ornithine and polyamine levels (65, 174)
3) NOS2 inhibitors: decrease NO formation (65, 202)
4) Phosphodiesterase-5 : reduce A1 and NOS2 expression (193)
5) Cyclooxygenase 2 inhibitors: reduce A1 expression and MDSC number (172, 218)
B. Reducing l-arginine availability to tumors auxotrophic for l-arginine (e.g., melanoma, hepatic carcinoma, acute lymphoblastic leukemias) by treatment with enzymes that metabolize l-arginine
1) Pegylated arginine deiminase (Peg-ADI) (12, 56, 108)
2) Pegylated arginase 1 (Peg-A1) (84, 144, 240)