Researchers in the Division of Hematology & Hematopoietic Cell Transplantation have identified a rare population of cells within small cell lung cancer tumors that may help establish novel critical targets for more effective anticancer therapies.

These cells express high levels of urokinase plasminogen activator receptor (uPAR), which is linked to poor prognosis and unfavorable outcomes. Research findings were published recently in the online journal PLoS ONE.

More than 200,000 Americans will be diagnosed with lung cancer this year, and experts expect small cell lung cancer, or SCLC, to account for about 13 percent of those cases. SCLC tends to spread widely throughout the body, especially to bone marrow and the brain, and is one of the most aggressive types of lung cancer, with uniformly poor prognosis.

Margarita Gutova, M.D., a post-doctoral research fellow in the lab of Karen S. Aboody, M.D., in the Division of Hematology & Hematopoietic Cell Transplantation, led the research team that identified this rare population of uPAR-expressing cells. Gutova noted the cells displayed progenitor cell-like properties and resistance to 5-fluorouracil, cisplatin and etoposide — drugs used to treat many cancers, including SCLC.

“To improve treatments for cancer, we must identify the drug-resistant subpopulation of cells within the tumor and target those cells by more effective and novel interventions,” Gutova said.

Previous studies had suggested the presence of a rare population of cells in solid tumors and leukemia that possess cancer stem cell-like properties and are able to regenerate and propagate the tumor. Researchers believe that these cells may be the underlying cause of tumor recurrence after therapy. 

Future studies in animal models will address whether the uPAR-positive cells are responsible for primary tumor growth and formation of distant metastases in SCLC. 

Co-authors included Aboody, Chu-Chih Shih, M.D., Joseph Najbauer, Ph.D., Anna Gevorgyan, M.D., Marianne Z. Metz and Yehua Weng.