- Posted Thursday February 2, 2012
Combination drug therapy urged to battle lung cancer
TGen-VARI study of protein JAK2 published by Public Library of
PHOENIX, Ariz. - Feb. 2, 2012 - Combination drug therapy may be needed to combat non-small cell lung cancer (NSCLC), according to a study by the Translational Genomics Research Institute (TGen) and Van Andel Research Institute (VARI).
The study, "STAT3 is Activated by JAK2 Independent of Key Oncogenic Driver Mutation in Non-Small Cell Lung Carcinoma," was published online today, Feb. 2, 2012, by the Public Library of Science (PLoS) ONE.
The study found that in NSCLC - the most common form of lung cancer - that the STAT3 gene is activated in some NSCLC cell lines by the JAK2 protein. This signaling can play a crucial role in tumor-cell behavior that may not be effectively inhibited by drugs that selectively target these mutations, the study concluded.
"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, a partnership between TGen and Scottsdale Healthcare that treats cancer patients with promising new drugs.
The JAK2 protein can activate the gene called STAT3, part of a family of genes that provide instructions for making proteins that are part of the essential chemical signaling pathways that control growth and development in cells. STAT3 has been found to be overactive in cases of several types of cancer, including breast, prostate, pancreas, leukemia and lymphoma.
In laboratory tests involving seven NSCLC cell lines, the TGen-VARI study found that STAT3 was activated in some cell lines by JAK2, independent of key oncogenic, or potentially cancer-causing, 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. VARI is TGen's affiliate in Grand Rapids, Mich.
This study, funded by a TGen-VARI integration grant, should benefit future lung cancer research because of the study's clinically annotated tissue microarray, MacKeigan said.
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About Van Andel Institute
Established by Jay and Betty Van Andel in 1996, Van Andel Institute (VAI) is an independent research and educational organization based in Grand Rapids, Mich., dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. Van Andel Education Institute (VAEI) is dedicated to strengthening science education and preparing and motivating individuals to pursue science or science-related professions. Van Andel Research Institute (VARI), the research arm of VAI, is dedicated to probing the genetic, cellular and molecular origins of cancer, Parkinson's and other diseases and working to translate those findings into effective therapies. This is accomplished through the work of over 200 researchers in 18 on-site laboratories and in collaborative partnerships that span the globe. VARI is affiliated with the Translational Genomics Research Institute, (TGen), of Phoenix, Arizona. For more information, visit: www.vai.org.
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