Attempts at treatment for cancer cells with constitutively phosphorylated STAT5 have included both indirect and direct inhibition of STAT5 activity. While more medicinal work has been done in indirect inhibition, this approach can lead to increased toxicity in cells and can also result in non-specific effects, both of which are better handled by direct inhibition.
Indirect inhibition targets kinases associated with STAT5, or targets proteases that carry out terminal truncation of proteins. Different inhibitors have been designed to target different kinases:
* Inhibition of BCR/ABl constitutes the basis of the functioning of drugs like imatinib
* Inhibition of FLT3 is carried out by drugs like lestaurtinib
* Inhibition of JAK2 is carried out by the drug CYT387, which was successful in preclinical trials and is currently undergoing clinical trials.
Direct inhibition of STAT5 activity makes use of small molecule inhibitors that prevent STAT5 from properly binding to DNA or prevent proper dimerization. The inhibiting of DNA binding utilizes RNA interference, antisense oligodeoxynucleotide, and short hairpin RNA. The inhibition of proper dimerization, on the other hand, is brought about by the use of small molecules that target the SH2 domain. Recent work on drug development in the latter field have proved particularly effective.