SARI highlights a previously unrecognized molecular pathway underlying the antitumor action of interferon.
Researchers have identified a new anti-tumor gene called SARI that can interact with and suppress a key protein that is overexpressed in 90% of human cancers.
The scientists discovered the new gene using subtraction hybridization. SARI, which is induced by interferon (IFN), was found to suppress growth and survival of tumor cells by interfering with the action of cancer cell molecules that drive cell division and promote survival.
The investigators delivered SARI to cancer cells using a virus, and the infected cancer cells subsequently stopped dividing and died. Currently, IFNs are relevant in the clinical treatment of a number of solid tumors and hematological malignancies either as a monotherapy or as an adjuvant to chemotherapy of radiotherapy.
“Additionally, IFNs are powerful immune-modulating agents that contribute to the immune response to cancer and they are effective inhibitors of new blood vessel formation, which is obligatory for the growth of both primary and metastatic cancers.” says Paul B. Fisher, Ph.D., professor in the VCU School of Medicine and lead investigator of the study.
“We have uncovered a new way by which interferon can induce antitumor activity. The identification of SARI also provides a new potential reagent for the selective killing of tumor cells.”
“The present study indicates that interferon can suppress cancer growth by inhibiting expression of a cancer-dependent transcription factor that controls genes that regulate cancer cell growth. The SARI gene may provide selective gene therapy applications for cancer. It could also prove amenable for inhibiting proliferative disorders that depend on AP-1 activity.”
The team, composed of researchers from Virginia Commonwealth University, Immunomedics, Mount Sinai School of Medicine, and Enzo Biochemicals is now developing improved approaches to more effectively target the delivery of SARI. The study can be found published online in the December 8 issue of PNAS.
