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Targeting STAT3 in cancer: how successful are we?Yue P; Turkson JExpert Opin Investig Drugs 2009[Jan]; 18 (1): 45-56BACKGROUND: Aberrant activation of the signal transducer and activator of transcription (STAT)3 occurs in many human tumors. Moreover, studies utilizing genetic and pharmacological approaches to modulate constitutive STAT3 activity have provided compelling evidence for the critical role of aberrant STAT3 activity in malignant transformation and tumor progression, and thereby validated STAT3 as a novel cancer drug target. OBJECTIVE: This review is intended to be a full coverage of the efforts to develop direct STAT3 inhibitors and will provide a discussion on the inhibitory modalities developed to date. METHODS: Review of the literature focused on the modalities and mechanisms that directly target and inhibit the STAT protein or its functions. RESULTS/CONCLUSION: While a variety of STAT3 inhibitors have been identified that induce antitumor cell effects in vitro and in vivo, the landscape remains murky. With a few exceptions, most of the STAT3 inhibitors reported to date have not undergone an in vivo efficacy, pharmacology or toxicity testing. Also, there is no evidence, per the published literature of an impending clinical development for the few agents that were reported to exhibit in vivo efficacy. Overall, there is the need for a reassessment of the ongoing strategies to target STAT3 intended not only for refinement, but also for incorporating some new technologies to strengthen our efforts and ensure the success - sooner, rather than later - of identifying suitable anti-STAT3 agents for development into clinically useful anticancer therapeutics.|Animals[MESH]|Antineoplastic Agents/therapeutic use[MESH]|Humans[MESH]|Neoplasms/*drug therapy/genetics/*metabolism[MESH]|Oligonucleotides/genetics/therapeutic use[MESH]|RNA Interference[MESH]|STAT3 Transcription Factor/*antagonists & inhibitors/genetics/*metabolism[MESH]|Signal Transduction/drug effects[MESH] |
