Moving Cancer Stem Cells toward the Clinic
The science of cancer stem cells and how the cells might be used to prevent and detect cancer was the focus of a workshop last week on the NIH campus. The meeting was sponsored by NCI's Division of Cancer Prevention (DCP).
Several hundred researchers heard presentations on what is known - and not known - about the molecular biology of cancer stem cells. Experts discussed genetic and epigenetic alterations, signaling pathways, and influence of the tumor microenvironment on cancer stem cells.
Many researchers were enthusiastic about one day using cancer stem cells in the clinic. But they acknowledged that a lack of cancer stem cells (and patient samples) is preventing the field from exploring basic questions, such as the origins of these cells.
"The meeting reinforced the view that we need to develop technologies to isolate and characterize cancer stem cells," said Dr. Sudhir Srivastava of DCP. "Time and again people talked about having cell lines and culture systems so that more laboratories can study these cells."
Recent studies have supported a role for cancer stem cells in early detection, noted Dr. Srivastava, who heads the Cancer Biomarkers Research Group. But the studies have not been replicated because of a lack of adequate cancer stem cell samples from patients.
Cancer stem cells are hard to isolate because they are so rare - perhaps as few as one tumor cell in a million. The first such cells were discovered in patients with leukemia in 1997. More recently, the cells have been reported in breast, colon, and brain tumors.
Like the stem cells that repopulate adult tissues, cancer stem cells are thought to perpetuate themselves while also giving rise to diverse types of tumor cells.
In a keynote address, Dr. Michael Clarke of Stanford University said that it will be important to have diagnostic tests that can identify precancerous lesions. By the time cancer stem cells develop it is often too late to help the patient, he noted.
Dr. Clarke also stressed the critical need to understand the mechanisms by which cells escape the normal constraints on self-proliferation.
Another keynote speaker, Dr. Stewart Sell of the Ordway Research Institute, discussed how the tumor microenvironment may influence the behavior of cancer stem cells. The surrounding environment may be as important as the intrinsic properties of the cancer stem cell, he said.
He and others discussed the need to characterize genetic pathways that are deregulated in cancer stem cells, particularly those involved in self-renewal. This could lead to strategies for identifying and blocking key signals in mutant stem cells.
Cancer stem cells could also be targets for drugs to prevent cancer in patients at risk of the disease, including those with premalignant lesions, commented Dr. James Crowell, who heads NCI's Chemopreventive Agents Development Research Group.
The need for cancer stem cell markers was a recurrent theme. Many researchers said that multiple markers may be required to capture the genetic diversity of cancers.
Building on the success of the workshop, DCP is consulting with experts on how best to support basic research on cancer stem cells that can be translated into clinical tools.
Drs. Jacob Kagan and Levy Kopelovich of DCP, who organized the workshop, are writing a summary of the meeting and recommendations for publication.
— Edward R. Winstead