Life’s Work Uncovers Genetic Clues to Treating Lung Cancer

Ralph Arlinghaus

Ralph Arlinghaus, Ph.D., transformed a personal tragedy more than 40 years ago into a research career that has uncovered information about how c-Abl kinase protein contributes to one type of leukemia and breast cancer and may be critical to creating targeted therapies for non-small cell lung cancer (NSCLC) as well.

Dr. Arlinghaus’ current research, funded by the American Lung Association, is focused on how c-Abl kinase, which is normally “silent” but is activated in some NSCLC cells, contributes to the abnormal growth of these cancer cells. The c-Abl protein is activated, in part, due to a defect in the FUS1 gene occurring in about 80 percent of non-small cell lung cancer patients.

The project grew out of Dr. Arlinghaus’ continuing motivation to help thunderstand ways to treat chronic myeloid leukemia (CML), which claimed the life of his young wife in 1967, and to provide new ways to treat cancers like NSCLC. Dr. Arlinghaus, who refocused his career from that of a chemist working on viral diseases of cattle to a cancer researcher, is Professor and Chair, Department of Molecular Pathology at the University of Texas MD Anderson Cancer Center.

NSCLC cells that have activated c- Abl may also secrete a small glycoprotein called lipocalin 2. Dr. Arlinghaus has previously researched the role of this protein for breast cancer and CML metastases. “We believe there’s an important connection in metastatic events in non-small cell lung cancer, and that the activation of c-Abl and the secretion of lipocalin 2 allow the metastatic spread of tumor cells. We have similar findings for CML and breast cancer and possibly liver cancer. My hope is that we can demonstrate the secretion of lipocalin 2 in non-small cell lung cancer as a critical aspect of metastasis as well.”

His American Lung Association-funded research may lead to a potential new target for lung cancer therapy and might contribute to the development of more advanced methods of early detection to effectively treat some forms of lung cancer. “I am very excited about this research because we may be able to help in the treatment for NSCLC cancer patients, since there are so few approaches that are effective now,” Dr. Arlinghaus says. “We are also exploring ways to make cells dormant to the point where the immune system is able to control the residual cancer cells in the body. Creating these targeted therapies could be so much less toxic for the body, but it is incredibly complex and difficult to achieve.”

New Lung Cancer Treatment Clinical Trials Under Way

American Lung Association researcher Alan P. Fields, Ph.D., and his team are conducting a clinical trial on a potential new therapy for lung cancer. Working under a recent American Lung Association/LUNGevity Foundation Lung Cancer Discovery Award, Dr. Fields discovered not only a major oncogene responsible for lung cancer development in mice, but also that a drug once used to treat arthritis shows promise as a targeted therapy inhibiting the gene in some types of lung cancer. A Phase I clinical trial found that the drug, aurothiomalate (ATM), was well tolerated by lung cancer patients. Dr. Fields is planning to soon start a Phase II trial to look at the effectiveness of the drug in combination with another targeted agent as a treatment for lung cancer.

“With five-year survival rates for lung cancer at only 15 percent, the need for new treatments is critical,” says Charles D. Connor, ALA President and CEO. “We are committed to finding a cure for lung cancer, and are grateful for our collaboration with LUNGevity Foundation on this important effort.”