Threshold

When cancer is treated with radiation or chemo, or even the up and coming antibody therapeutics, some cancer cells may survive. These surviving cancer cells contribute to the much more malignant and harder to manage recurrent disease that results in death. The reason why certain cells survive anti-cancer treatments is thus far unknown, the best that science and biotechnology can provide is that tumor cells are heterogeneous, and because of that heterogeneity, certain cells in the tumor are resistant to anti-cancer treatments. The reason for the inability for science to investigate the biology behind drug resistance lies in two places. One, the inability, thus far, for science to obtain true "cancer" cells suitable for in vitro experimentation. Second, the inability to correctly reproduce the selective pressures exerted upon the tumor cells in vivo.

The first of the two problems, the concern of the true "cancer" cell, is currently being pursued by numerous academic and industry concerns. Central to this is obscures the push for stem cell research, the hope of deriving a truly "normal" human cell "line" that can be instigated to become cancerous and allow for the study of the mechanism of tumorgenesis de novo.

The second problem, the problem of exerting the correct selective pressure, is related to the first concern. However, there is a deeper theoretical question attached to it. Were a correct cell line to be derived, what is the correct selective pressure? In that, a drug, used at a higher and higher dose, will eventually wiped out all cells exposed to it. It is a numbers game. At a small dose, the cell can adapt by changing the rate of molecule movement and the rate of metabolism to overcome a stressed or minimally inhibited process. At a moderate dose, the cell can further tax it's trafficking mechanics or alternatively, toggle it's metabolite dependence to escape the handicap dealt by an altered or inhibited process. When the dose becomes overwhelming, however, the processes sensitive to the selective pressure can no longer be ignored or by-passed, resulting in death. This dose sensitivity is called the threshold.

As we are constantly astride the threshold to cancer therapies, the threshold stares back and mocks us.