I've been pointing out advances at the intersection of cancer and stem cell research in past months; it does look promising, especially now that we're moving into the era of "give me a clear marker on the cell and I can kill it safely with modern biotechnology." A large research infrastructure is presently dedicated to uncovering markers for stem cells as a part of learning how to use them for regenerative therapies - if that is also a path towards the defeat of cancer, so much the better.

It is plausible that our cancers are driven by errant stem cells, and that advancing biotechnology will let us effectively deal with those cells sooner rather than later. Perhaps the most encouraging possibility is that the bulk of cancers, or even increased risk of cancer, might come down to just a small cluster of possible mutations or epimutations:

When the teams compared patterns of gene activity in stem cells from healthy and cancerous tissue they found that those from cancers were often locked in a state in which they carry on multiplying as primitive stem cells, instead of maturing into specific tissues. ... When they're in this state they divide more, and in the process may accumulate additional mutations which ultimately turn them cancerous." From the original paper: "Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes required for differentiation. We report that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation.

If cancer results - or even only mostly results - from a single identifiable class of changes in stem cells, there won't be much cancer in the world 20 years from now. We can hope.

However, it is worth airing the skeptical viewpoint - which starts with the observation that next to nothing in the world of biochemistry is as simple as we would like it to be. Cells are hugely complex pieces of machinery, and that complexity is vastly multiplied by the ongoing interactions and lifecycles of trillions of cells in your body. The cancer stem cell skeptic acknowledges the research demonstrating the importance of stem cells to sustaining a cancer, but points out:

• Cancers are characterised by extremely rapid mutation and adaptation as the result of their fast growth and aggressive cell replication
• This is one of the reasons cancers are so hard to treat with more brute force techniques such as radiation and chemotherapy - cancer cell populations very quickly evolve resistance to most of what can (reasonably) safely be tried as a therapy in this arena
• There is no reason per se that this rapid mutation cannot include the mutation of normal cells into stem cells or stem-like states sufficiently empowered to support the cancer
• It is possible that many combinations of a small number of mutations exist to produce cells sufficiently stem-like to support a cancer - and are therefore likely to be created in a rapidly mutating cancer
• Therefore targeting stem cells may or may not be a more effective form of therapy in and of itself - a cancer might just evolve its way into replacing them with one of many different sorts of stem cells or stem-like cells based on new markers and mutations, just as it can evolve resistance to specific toxins

Given the present rate of progress, I think it unlikely that any debate over the effectiveness of identifying and targeting cancer stem cells will remain unsettled past 2012, five years from now. The first therapies based on present day approaches in the laboratory should be somewhere in late trials by that time, and a healthy weight of first results in humans already in hand.

Technorati tags: biotechnology, cancer research

Posted by Reason at January 16, 2007 9:07 PM | TrackBack (3)