SciAm to Stem Cancer

The July issue of Scientific American just arrived in the mail today. Among other interesting pieces, it has an article on mechanisms of cancer, a subject that I was thinking about recently. Michael F. Clarke and Michael W. Becker have produced a very convincing summary of research on stem cells and their relation to cancer. They contend that the treatment of many cancers is partial and doomed to fail because it addresses only the end result of the development cascade. Malfunctioning stem cells are the real culprits.

Stem cells are, of course, those undifferentiated cells that are capable of reproducing and programmed to produce specific tissue types in specific situations. The surrounding somatic cells, called a niche, send signals to the stem cell, sometimes causing it to reproduce. Each time stem cells split into two cells, one cell is a perfect copy and the second is more specialized. They spin off such daughter cells in a very choreographed manner, where progressive specialization and carefully controlled reproduction are used to create a non-reproducing final product.

Injuries and insults to the stem cell, such as radiation or copy errors, may cause its programming to change. The aberrant stem cell may appear normal, and so may its daughter cells of the first several generations, but the abnormal end result may lose its self-regulation capacity. There may even be a feedback process by which the abnormal niche cells signal for aberrant stem cells to reproduce. If the tissue is detected as abnormal and medically treated, the treatment will probably be designed to target abnormal growth only and to preserve surrounding healthy cells. Those "healthy" cells, however, may harbor the true source of the cancer. Maybe we need to attack the cannon rather than the shells.

Clarke and Becker outline four scenarios of malignancy. A) The cancerous stem cell either induces or waits for a change allowing proliferation of the niche cells, which then call for more abnormal stem cells. B) A change in the stem cell allows it to adapt to other, perhaps inappropriate, niches. C) Mutation in the stem cell causes it to ignore signals from the niche cells. D) Progenitor cells, already holding one or more mutations from the damaged stem cell, independently develop another mutation that pushes them over the edge into self-reproduction.

The only weaknesses I see in the theory are 1) it struggles to explain the time lapse between the original trigger and the inception of the cancer, and 2) it doesn’t explain the unexpected self-defense mechanisms that some cancers develop.

6/16/2006 12:46 AM