The pathway is known as NF-kB and a variety of chemotherapies and cytokines used in the treatment of cancer are known to activate its signaling. The current studies were undertaken to assess if INGN 241 had a similar effect.
“These studies demonstrate that mda-7, the active component of INGN 241, activates NF-kB in lung tumor cells,” said Rajagopal Ramesh, associate professor in the Department of Thoracic and Cardiovascular Surgery at MD Anderson Cancer Center.
“Although the potent effects of mda-7 ultimately overcome NF-kB and lead to cancer cell death, these studies show that inhibition of NF-kB enhances the anticancer activity of INGN 241. This suggests that combining INGN 241 with NF-kB inhibitors could yield improved clinical effects.”
Results of tissue culture studies indicated that NF-kB levels in lung cancer cells were higher following administration of INGN 241. Additional cell culture analyses demonstrated that INGN 241 inhibited cell proliferation in cells with activated NF-kB, and that this effect was enhanced with inhibition of NF-kB. INGN 241 activity also was enhanced in animal models of lung tumors engineered to inhibit NF-kB activation.
INGN 241 is being tested in a phase II trial for patients suffering from advanced melanoma and in a phase III trial in combination with radiation therapy in solid tumors.