Developing Pharmacological Modulators of STAT Signaling
Erik A. Nelson and David A. Frank
As cancer continues to cause over 500,000 deaths per year in the United States alone, it is clear that the cytotoxic drugs commonly in use for cancer treatment are not adequately effective. As we have increased our understanding of the molecular abnormalities in cancer cells, the opportunity arises to target these specifically to achieve greater efficacy and decreased toxicity. Kinase inhibitors have begun to show activity in a number of tumors, but with a few exceptions, the kinases activated in a given tumor are not known. Since STATs are key mediators of many activated tyrosine kinases, developing inhibitors of these transcription factors holds the promise to have widespread applicability in cancer. In addition, drugs that can activate specific STATs may have clinical benefit in certain circumstances as well. In recent years, a number of strategies have been used to develop modulators of STATs for therapeutic purposes and these drugs may be important additions to the repertoire of cancer therapies.