Stem cells: the role of cancer-initiating cells in diagnosis and treatment

Recent discoveries about the role of stem cells in cancer have altered the landscape of cancer research. As scientists learn more their cancer-initiating properties, stem cells are emerging as potential therapeutic targets for many types of cancers. Studies presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, report stem cell discoveries related to pancreatic, bladder, ovarian, and breast cancer, and glioma.

Rasheed ZA, et al. The functional stem cell marker aldehyde dehydrogenase enhances pancreatic cancer stem cell isolation and correlates with clinical prognosis: Abstract 5000

Researchers have identified aldehyde dehydrogenase as a new marker for the presence of pancreatic cancer stem cells, a finding with potential for the development of targeted therapy. Pancreatic cancer is highly aggressive and largely resistant to current therapies. Researchers believe that pancreatic cancer stem cells may be responsible for resistance to chemotherapy.

“Cancer stem cells have emerged as a potential therapeutic target, but the development of effective therapies requires the identification and isolation of highly purified cell populations,” said Zeshaan Rasheed, M.D., Ph.D., a researcher at Johns Hopkins University. Analyzing human pancreatic tumor samples, Rasheed and colleagues found that each contained a small population of cells that expressed aldehyde dehydrogenase, and that these cells showed a greater capacity for growth compared with the cells that did not express aldehyde dehydrogenase. Capacity for growth is among the definitive characteristics of stem cells.

Previous research identified CD24+ and CD44+ cells as pancreatic cancer stem cells, Rasheed says. Rasheed and colleagues found that cells that were CD24+, CD44+, and expressed aldehyde dehydrogenase had a significantly greater potential for reproduction, another definitive characteristic of stem cells, and may be responsible for pancreatic cancer metastasis.

The authors also found that the presence of cells positive for aldehyde dehydrogenase was significantly associated with poorer overall survival. Specifically, patients with these cells lived an average of 14 months after diagnosis compared with 18 months for those without the cells.

“These results suggest a direct link between cancer stem cells and patient outcomes,” said senior author William Matsui, M.D., of Johns Hopkins University.

Vlashi E, et al. Prospective identification, tracking and targeting of cancer-initiating cells in breast cancer and glioma via low proteosome activity: Abstract 4997

Identification of cancer stem cells remains a challenge at the microscopic level, but researchers have concluded that low proteosome activity can be an effective marker to isolate these cells from the wider population and track their response to treatment in vitro and in vivo.