Immunosuppressives seem to hold exciting promise in cancer treatment. One particular antibiotic could become an anti-cancer agent too, it is hoped.
Immunosuppressive drugs can form a part of treatment of autoimmune diseases like rheumatoid arthritis, lupus or HIV, which arise from inappropriate immune responses. In such instances, the body's immune system attacks the body, instead of attacking foreign cells. It is to inhibit such a response, the immunosuppressives are pressed into service. Such drugs are also used in organ transplant.
When an organ, such as a liver, a heart or a kidney, is transplanted from one person (the donor) into another (the recipient), the immune system of the recipient triggers the same response against the new organ it would have to any foreign material, setting off a chain of events that can damage the transplanted organ. The immunosuppressant drugs greatly decrease the risks of rejection, protecting the new organ and preserving its function.
Now a study at the Indiana University School of Medicine determined that the antibiotic compound tautomycetin targets an enzyme called SHP2, which plays an important role in cell activities such as proliferation and differentiation. Interestingly, SHP2 mutations are also known to cause several types of leukemia and solid tumors. The findings were reported in the Jan. 28, 2011, issue of the journal Chemistry and Biology
The potential for developing anti-cancer agents grew out of an attempt to determine how the compound, tautomycetin, exerts its immune suppression activities, said Zhong-Yin Zhang, Ph.D., Robert A. Harris Professor and chairman of the Department of Biochemistry and Molecular Biology.
The finding is also encouraging because SHP2 is a member of a large family of enzymes called protein tyrosine phosphotases (PTPs), which are important in the signaling processes that control all essential cellular functions. Dysregulation of PTP activity has been linked to several human diseases, including cancer, diabetes, and immune dysfunctions. But their makeup has made it difficult to find potential drugs to act on them, characteristics that have labeled the PTPs as "undruggable," Dr. Zhang said.
"So we have identified a lead — a natural product produced by the bacteria Streptomyces
— that should serve as a foundation for the development of therapeutic agents for a large family of protein tyrosine phosphotase targets. Until now these targets, including SHP2 for leukemia and other cancers, have been deemed undruggable," he said.
Dr. Zhang is a member of the Indiana University Melvin and Bren Simon Cancer Center. Funding for the research was supplied by the National Institutes of Health.