Clonal Evolution or Cancer Stem Cells?
Nothing biological is ever as simple as it could be - and it usually isn't as simple as your scientific predecessors hoped it to be either. So here we are again, revisiting skepticism on the whole cancer stem cell issue:
According to a longstanding cancer model, known as "clonal evolution," tumors arise from normal cells that mutate and generate abnormal offspring that also mutate, forming a mass of genetically varied cancer cells. However, there has been a new wave of interest in an alternative explanation - that tumors are initiated and driven by a single, abnormal type of adult stem cell found in, for example, breast tissue, resulting in a population of genetically identical tumor cells. Moreover, several pathways and genes required for normal stem cell function are activated in cancer cells and play essential roles in the development of tumors.
It would be a wonderous development if it turns out that a significant fraction of cancers are driven by errant stem cell populations - because that would mean (a) we are very close to being able to efficiently detect and destroy them, (b) the vast influx of resources into the field of regenerative medicine and stem cell research will also contribute to meaningful cures for cancer.
In effect, this is one aspect of asking just how hard it will be to transform cancer into a managed chronic condition. Easier than we thought if it's all stem cells going bad in clearly identifiable ways ... but that may not the case. Nothing is ever simple in biology, remember? I looked at the skeptical viewpoint on cancer stem cells a little while back, and here is a little more context in terms of present research:
According to the cancer stem cell hypothesis, the few self-renewing stem cells that fuel the cancer are difficult to kill, and their persistence may explain why tumors so often recur following successful therapy. In 2003, scientists purified what they proposed were breast cancer stem cells from patients’ tumors. The distinctive molecule, or marker, on the cells’ surface, known as CD44+, was identical to the marker on normal breast cells. When injected into mice lacking an immune system, the CD44+ cells demonstrated the ability to initiate breast tumors. The scientists also found closely related cells with a CD24+ marker and suggested that they were offspring of CD44+ cells.The team led by Polyak and Michail Shipitsin, also of Dana-Farber and HMS, used gene activity analysis to clarify the relationship of the two cell types. They generated gene libraries from CD24+ and CD44+ cells purified from normal mammary epithelium and fluids within the chest, and from primary invasive tumor samples collected from breast cancer patients.
The findings, the scientists reported, fit more closely with the clonal model than the cancer stem cell hypothesis. That is, the CD24+ cells were very similar to the CD44+ cells, but not always genetically identical - which they would have been if the CD44+ cells were true stem cells and the CD24+ their offspring.
"Although CD44+ cells appear to express many stem cell markers, the genetic difference between CD24+ and CD44+ cells within a tumor questions the validity of the cancer stem cell hypothesis in breast cancer, and suggests clonal evolution involving intra-tumoral heterogeneity as an alternative explanation," the authors wrote.
However it happens, we must see cancer wrestled into control as a part of living much longer lives through advanced medicine. Easy or hard, that goal must be accomplished - otherwise the only benefit resulting from the defeat of other age-related conditions will be a much greater chance to experience death by cancer.
Technorati tags: cancer research