- Posted Thursday July 7, 2011
Researchers examine how genes and proteins affect therapeutic
PHOENIX, Ariz. - July 7, 2011 - The Translational Genomics Research Institute (TGen) is presenting two key studies, including one today, at the 14th World Conference on Lung Cancer, July 3-7 in Amsterdam.
One study, presented July 4, involved a gene called GLI1, which may limit the effectiveness of the most common combination chemotherapy given to patients with small cell lung cancer (SCLC).
Another study, presented today, July 7, suggests that combination drug therapy may be needed to combat non-small cell lung cancer (NSCLC) - the more common type of lung cancer - when patients have elevated levels of a protein called JAK2.
Both studies will be presented at the Amsterdam conference, which is sponsored by the International Association for the Study of Lung Cancer (IASLC). The association hosts an international lung cancer meeting every two years. Both studies also will be published in a special supplement of the Journal of Thoracic Oncology.
GLI1 may compromise chemotherapy
In the study involving GLI1, laboratory tests of six SCLC cell lines showed that GLI1 can play an important role in resistance to the drugs cisplatin and etoposide, which given together are the standard first-line chemotherapy for SCLC.
"Resistance to chemotherapeutic drugs is particularly crippling in SCLC," said Dr. Glen Weiss, Co-Unit Head of TGen's Lung Cancer Research Laboratory, who led the research in both studies presented at the conference. "We are optimistic that this GLI1 study will lead to more detailed examinations that will provide a better way of treating patients."
Next steps include using RNA interference tests to validate the role of GLI1 and several related genes along the Hedgehog Signaling Pathway - a series of chemical reactions within a cell. The Hedgehog pathway contains genes that lead to GLI1, a known tumor-promoting gene. Weiss' team also plans to conduct tests on actual tumors from SCLC patients.
VARI joins TGen in JAK2 study
The Van Andel Research Institute (VARI), TGen's affiliate in Grand Rapids, Mich., joined TGen in conducting the JAK2 study.
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 cancer-causing mutations.
"JAK2-STAT3 signaling plays crucial roles in tumor-cell behavior that may not be effectively inhibited by drugs that selectively target these mutations," Dr. Weiss said. "This suggests that there may be a potential role for combination therapy, so you have a better chance of knocking out a NSCLC tumor, or keeping it at bay."
Dr. Jeff MacKeigan, Head of VARI's Laboratory of Systems Biology, said this yearlong study, funded by a TGen-VARI integration grant, should benefit future lung cancer research because of the study's clinically annotated tissue microarray.
"Our human tumor samples may be used for meaningful exploratory research on other key signaling pathways in NSCLC," MacKeigan said.
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Founded in 1972, the International Association for the Study of Lung Cancer (IASLC) is an international organization of nearly 3,000 lung cancer specialists spanning 80 countries. IASLC members work towards developing and promoting the study of etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and other thoracic malignancies. IASLC's mission is to enhance the understanding and education of lung cancer to scientists, members of the medical community and the public. In addition to the biannual meeting, the IASLC publishes the Journal of Thoracic Oncology, a prized resource for medical specialists and scientists who focus on the detection, prevention, diagnosis and treatment of lung cancer. For more information, visit: www.2011worldlungcancer.org.
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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