Cancers 2014, 6(1), 494-525; doi:10.3390/cancers6010494

Genetic Interactions of STAT3 and Anticancer Drug Development

Received: 13 November 2013; in revised form: 18 February 2014 / Accepted: 20 February 2014 / Published: 6 March 2014
(This article belongs to the Special Issue STAT3 Signalling in Cancer: Friend or Foe)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors.
Keywords: genetic interaction; cancer; drug development; STAT3; Ras; EGFR; redox; reactive oxygen species; synthetic lethality
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MDPI and ACS Style

Fang, B. Genetic Interactions of STAT3 and Anticancer Drug Development. Cancers 2014, 6, 494-525.

AMA Style

Fang B. Genetic Interactions of STAT3 and Anticancer Drug Development. Cancers. 2014; 6(1):494-525.

Chicago/Turabian Style

Fang, Bingliang. 2014. "Genetic Interactions of STAT3 and Anticancer Drug Development." Cancers 6, no. 1: 494-525.

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