Table 1.

Therapeutic strategies under investigation with the intent of abrogating Stat3-mediated signaling

Approaches	Mechanism	References
Stat3 ablation	Preclinical in vivo studies suggest that ablation of Stat3 in tumor cells or tumor-associated immune cells decreases tumor progression	Kortylewski et al. (2005), Wang et al. (2004), Yu and Jove (2004), and Yu et al. (2007, 2009)
JAK inhibitors	Use of these agents (i.e., AG490, WP1066, AZD1480) decreases Stat3 activation and augments the tumor-associated immune response in preclinical models of both hematologic and solid tumors	Burdelya et al. (2002), Fujita et al. (2008), Hussain et al. (2007), Kong et al. (2008), Kong et al. (2009), and Nefedova et al. (2005)
Other tyrosine kinase inhibitors	Inhibitors of fusion proteins (i.e., products of NPM/ALK or BCR-ABL) Both directly and indirectly inhibit activation of Stat3 Agents such as sunitinib decrease recruitment of Tregs and MDSC to sites of tumor in a Stat3-dependent fashion	Kasprzycka et al. (2006), Larmonier et al. (2008), Ozao-Choy et al. (2009), and Xin et al. (2009)
CpG-siRNA	Stat3 siRNA linked to the Toll-like receptor agonist 9 (TLR9), CpG, both silences genes in TLR9(+) myeloid cells and decreases the Stat3-mediated immune response; in preclinical models, a marked antitumor effect is observed	Kortylewski et al. (2009a, b)