Assessment of cancer stem cells in clinical trials

by Alexey Bersenev on April 28, 2010 · 0 comments

in cancer

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It was noted at the 2010 AACR annual meeting, which finished just last week, that in era of started clinical trials targeting cancer stem cells (CSC), we really need criteria for assessment of anti-CSC therapy efficacy. How can we make sure that we targeted CSC precisely and our therapy really works?

1. Markers
The first obvious and easiest test could be assessment by markers. Potential candidates: CD133, CD44, ALDH. The problem is that in many indications these discovered markers are not validated, because reports are very controversial. For example, CD133 controversy and more in general.

2. Size of tumor
Jeffery Rosen pointed out that tumor shrinkage doesn’t tell you anything about what happened to CSC population. There is a general assumption in the field, proven in some studies, that CSCs are a rare and drug-resistant population. So if, size of tumor is very indicative for efficacy of conventional therapy, it’s not the case for CSC.

3. Survival and rate of relapses
These criteria, potentially, could be the best for assessment of anti-CSC therapy. The problem is how to set it in time after therapy? Should we look at 1 or 5 or 10 years survival? How can we define “complete remission” or “minimal residual disease” in terms of CSC? With knowledge that relapse or disease recurrence could happen many years (5-15) after remission, we should set long-term survival as the main criteria of anti-CSC therapy efficacy. Unfortunatelly, in this case, a whole clinical trial can take 7-15 years.

4. Minimal residual disease
Tessa Holyoake, noted that we are coming to the realization that minimal residual disease (MRD) in leukemia is more likely associate with CSC. In this case should we apply leukemic stem cell markers (coupled with mutation) as diagnostic criteria of MRD? Currently MDR diagnostics is based on identification of bulk blood or leukemic cells carrying mutations (DNA, RNA tests). If CSC markers will be applied, what number or % of them with mutation should we consider as safe level of MRD? Should we keep them at “safe level” or aim to eradicate them?

5. Definitions
One of the problems in the field is absence of consensus about definitions. Donald McDonald gave an examples from literature covering anti-angiogenesis therapy. He said that many authors widely use term “tumor aggressiveness”, but with different meaning. Some groups use it to describe survival, some – number and size of metastasis, some – size of primary tumor. But in reality size of tumors and number of metastasis are not always correlate with survival and vice versa. This is exactly what we can expect from trials targeting CSC.

Overall, consensus for assessment of efficacy criteria is required for entering into a new and exciting era of CSC clinical trials.

twitter hashtags: #AACR10 / #cancerSC

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