<b>Chemotherapy and De-differentiation</b>

<b>[For further explanation of de-differentiation see the web page "Testing Your Tumor" on this site.]</b>

Differentiation is the process by which the original fertilized egg, and its descendants, change from being identical to each other to being different...e.g. hair follicle cells and muscle cells and nerve cells and blood cells... and so on. Differentiation refers to the process by which the cells become different from each other as they become more sophisticated, specialized types of cells.
 
In a cancer tumor, as the cancer cells accumulate more and more mutations, the specialized nature of the original cell is lost. For instance, if it originally had an estrogen receptor on its cell membrane, often that receptor is lost. The cell with more and more mutations loses its abilities because of those mutations, and becomes less specialized and more primitive. And as more and more damage accumulates, the cell becomes more and more primitive, aberrant, and bizarre. This process is called de-differentiation. It occurs in all cancers, it is inevitable, and it is a function of time, as it takes time to accumulate the mutations. It will usually occur more quickly in tumors with high reproductive rates, and can be hastened by chemotherapy or radiation. It might result in tumors that suddenly grow uncontrollably - even while being treated with chemotherapy AND radiation.

Treating LMS tumors with radiation or chemotherapy might increase de-differentiation in the surviving tumor cells. If LMS is treated by radiation or chemotherapy, there will almost always be surviving tumor cells. Increased de-differentiation could possibly result in aggressive, fast-growing LMS tumors, utterly unresponsive to chemotherapy or radiation. This is one of the risks of treating LMS tumors, and another reason to perhaps limit chemotherapy and radiation to specific situations where the benefits are clearly apparent, or clearly life-preserving. In other words...stop the cascade of metastases, and deal with later de-differentiation problems when and if they occur-LATER. Shrink the tumor so it can be surgically removed, and deal with late effects-LATER. Use the chemotherapy agents one by one, palliatively, to extend survival time. By all means, USE chemotherapy when it is clearly of proven benefit. But be aware that everything has a price, and increased de-differentiation may be part of the price for chemotherapy usage.