ATLANTA - With an estimated 20,000 in attendance, the 49th annual meeting of the American Society of Hematology ended Tuesday with a bang, not a whimper.
Tuesday's offerings might have been slightly lighter than the previous days, but they were certainly heavier in terms of importance.
The centerpiece of the day's events was a panel discussion on cancer stem cells, or those cells that have properties of adult stem cells, particularly the abilities to self-renew and differentiate into multiple cell types. Those cells persist in tumors as a distinct population that likely causes disease relapse and metastasis - they are the only cells capable of, by themselves, giving rise to new tumors.
John Dick, of the University Health Network in Toronto; Hans Clevers, of Hubrecht Institute in Utrecht, the Netherlands; and Craig Jordan, of the University of Rochester Medical Center, were the panelists discussing the stem cell topic.
The main concern regarding the cancer stem cell philosophy is if researchers are targeting the right kind of cell. Most of the existing cancer treatments are developed on animal subjects, where the treatments are able to promote tumor shrinkage and are deemed effective.
But animals don't provide a complete model of human disease. Some of the animal test subjects only have a short life span, not long enough to see if there is a tumor relapse, according to cancer stem cell studies. "We don't have enough markers in these blood cells to determine the phenotype," Jordan said. "Certainly there are a variety of different activation pathways [for the cancerous cells]."
Another issue comes from the fact that the efficacy of cancer treatments, in the initial stages of testing, often is measured by the amount of tumor mass it can kill off.
As cancer stem cells make up a very small proportion of the tumor, that doesn't necessarily select for drugs that act specifically on the stem cells. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate new cells. A population of cancer stem cells, which gave rise to it, remains untouched and may cause a relapse of the disease. "We seem to be holding on for the search of a 'magic bullet' in terms of treatment," said a member of the audience.
But according to the panelists, the development of a magic bullet or specific therapies that are targeted at cancer stem cells is still a good bit off, even though important strides have been made thus far.
The problem with targeting those cells can be found in the composition of normal tissue stem cells. Those stem cells are naturally resistant to chemotherapeutic agents - they have various pumps (such as MDR) that pump out drugs, DNA repair proteins, and they also have a slow rate of cell turnover (chemotherapeutic agents naturally target rapidly replicating cells).
Also, there has been a lot of research into finding specific markers, which may differentiate cancer stem cells from normal cancer cells, with some success. That may allow drugs to directly target the stem cells.
"The challenge is to collect a large amount of cells and interrogate these cells rigorously," Dick said. "There has to be an effort to bank large cells and then we'll be able to ascertain these models more properly."