What's Next for Cancer Stem Cells?
The concept of cancer stem cells has generated great excitement in the research community. These cells - the hallmark of which is resistance to therapy and the ability to self-renew and produce a differentiated population of daughter cells - have been identified in many solid and hematopoietic cancer types.
With the intention of supporting research in this new field, on November 1, we held the first NCI Stem Cell Mini-Retreat, where NCI and NIH researchers and extramural investigators gathered to learn from each other about the latest advances in stem cell research and to identify opportunities for collaboration that could significantly advance the field, expand translational opportunities, and leverage resources.
The implications of these cells for cancer treatment are enormous. Although relatively rare, with only about 1 out of 1,000 to 10,000 cells in any given tumor, their resistance to standard therapies and their proliferative potential make them a likely cause of many recurrences after seemingly curative treatment. Their plasticity and ability to survive a hostile environment through quiescence - the state of being dormant - are also thought to contribute to their metastatic potential.
As I mentioned in a previous column, new insights into the role of these cells in tumorigenesis and metastasis make this an excellent time to accelerate study in this field. One of the primary goals of the November 1 retreat was to identify the immediate impediments to rapid progress in cancer stem cell research.
In the area of basic research, participants highlighted the need to accurately identify these rare cells. Much of this identification will come from elucidating specific cell markers and aberrantly expressed signaling pathways, both of which also have implications for targeted therapy.
Speakers also discussed the current challenges in isolating and growing these cells, which are difficult to maintain in culture, and the pressing need for appropriate models to test therapies both in vitro and in vivo.
In the area of treatment, the crux of the discussion revolved around one major question: By identifying and blocking specific cell-signaling pathways, is it possible to nullify the "stemness" of these cells, leaving them vulnerable to treatment?
This question highlights other challenges. For example, cancer stem cells often cycle into a quiescent state, requiring identification of a stimulus to activate them before treatment. The design of clinical trials in this field will need to identify new methods to evaluate the success of anticancer stem cell therapies. Clearly we have a lot of work ahead of us. The final question posed at the retreat asked what NCI would do next to promote the necessary research in this field.
We have been inspired by the success of the Trans-NIH Angiogenesis Research Program (TARP) in promoting collaborations between investigators from many different disciplines, and hope to soon launch a similar trans-NIH stem cell biology and embryogenesis initiative, to facilitate the exchange of knowledge and technology both intramurally and extramurally.
NCI is now beginning the process of planning a multi-day symposium, hopefully on an annual schedule, to launch this new initiative. This type of symposium has been very helpful for TARP, and will let investigators identify opportunities for funding, resource sharing, and potential for collaborations.
Though the field of cancer stem cells is new, it holds great promise, and NCI is committed to supporting new research in this area.
Dr. John E. Niederhuber