Potential therapeutic target for tobacco-related lung cancers identified

Washington - Researchers have discovered that the immune response regulator IKBKE (serine/threonine kinase) plays two roles in tobacco-related non-small cell lung cancers.

Tobacco carcinogens induce IKBKE and, in turn, IKBKE induces chemotherapy resistance.

“IKBKE is a newly identified oconogene, a gene linked to cancer,” said study lead author Jin Q. Cheng, Ph.D., M.D., who studies genetic alterations and their molecular mechanisms in  cancer.

“In our study, we demonstrated that IKBKE is a STAT 3 target gene and is induced by tobacco. STAT3 is a signaling and transcription gene that is activated in various types of cancer and is  required for cell transformation,” he explained.

As a “transcription factor” STAT3 plays a key role in many cellular processes, such as cell growth and programmed cell death, or “apoptosis.”

“It has been well documented that STAT3 is activated by growth factors and environmental carcinogenesis, such as nicotine,” said Cheng.

“STAT3 directly binds to the IKBKE promoter and induces IKBKE transcription,” he added.

Tobacco smoke is the strongest documented tumor initiator and promoter in lung cancer. The underlying molecular mechanism is still largely unknown.

“IKBKE is induced by tobacco carcinogens and mediates tobacco action in promoting lung cancer cell survival. Armed with this knowledge, interventions targeting the IKBKE pathway could  be developed,” said Cheng. 

Cheng and his colleagues found that when STAT3 induces IKBKE expression, IKBKE's expression induces chemotherapy resistance. Conversely, “knocking down” IKBKE sensitizes cells  to chemotherapy, suggesting that there is a therapeutic role for targeting IKBKE.

The study was published in a recent issue of Oncogene.