When battling non–small cell lung cancer (NSCLC), combination drug therapy may be required, according to the study, “STAT3 is Activated by JAK2 Independent of Key Oncogenic Driver Mutation in Non-Small Cell Lung Carcinoma.” The research, by the Translational Genomics Research Institute (TGen) and Van Andel Research Institute (VARI), was published online February 2, 2012, by the Public Library of Science ONE.
The study found the JAK2 protein triggers the STAT3 gene in some NSCLC cell lines. “This suggests that there may be a potential role for combination therapy, so you have a better chance of knocking out select NSCLC tumors driven by STAT3-JAK2, or keeping it at bay,” said Dr Glen Weiss, co-unit head of TGen’s Lung Cancer Research Laboratory and Director of Thoracic Oncology at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare.
The gene, STAT3, provides instructions for the production of proteins, the essential chemical signaling pathways that determine growth and development in cells. STAT3 has been found to be overactive in several types of cancer, including breast, leukemia, lymphoma, pancreas, and prostate. According to the study, the JAK2 protein can activate the STAT3 genes.
In fact, in laboratory tests involving 7 NSCLC cell lines, the TGen-VARI study revealed STAT3 was triggered by JAK2 in some cell lines. This activation was independent of key oncogenic genes.
“JAK2-STAT3 signaling plays crucial roles in tumor-cell behavior that may not be effectively inhibited by drugs that selectively target these mutations,” said Dr Jeff MacKeigan, head of VARI’s Laboratory of Systems Biology.