[QUOTE=Captain Amazing]
Well, cancerous cells are different than non-cancerous cells (partly because they’re always reproducing). Among the changes are changes to the cell membrane (which is the outside of the cell…it’s the layer of lipids and proteins that surrounds the cell and holds it together). So you try to design a molecule that will bind with the proteins on the cell membrane of a cancerous cell and not with the proteins on the cell membrane of a non-cancerous cell.
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Yes, but most of these changes are quantitative in nature, not qualitative. A cancer cell may have several hundred thousand copies of a particular protein on its surface, while normal cells throughout the body have between none and a few thousand, depending on the cell type. But in addition, all cells will take up bulk fluid by pinocytosis. Therefore, the targeting of a drug to the cancer cells is never absolute. We can achieve a selectivity of around 1:10’000 in cell culture, that is, it takes a 10’000-times higher dose of the same compound to kill cells that don’t carry the tumor marker protein than to kill the tumor cells. It works ok in clinical trials when you can inject the drug directly into the tumor. But for a drug that can be injected into the bloodstream and that seeks out metastases throughout the body, we need even higher selectivity.
The problem is, you need to kill every last cell of the cancer, and you need to do so fast. Because, if some of the tumor cells survive the treatment, they are usually the cells that are most resistant to the treatment, and will grow to form tumors that are less sensitive to the drug. Since cancer cells tend to accumulate mutations, they can “evolve” to adjust to the treatment. With every new round of treatment you need, your chances of beating the disease decrease.
A tumor the size of a chickpea (1 gram) already contains around a billion cells, and you need to kill every single one of them. It is not enough to kill 99% or 99.9% or even 99.999%, but every single cell.
Targeting the drug to the cancer cells is an important step towards achieving the necessary discrimination between cancer cells and the most sensitive normal cells, but we will probably need a multi-stage approach to further increase the specificity. In addition, there is not one tumor marker present on all types of cancer, therefore different targeting moieties have to be found to address different types of cancer.
We are making progress, but it is a slow and tedious progress that is very unlikely to lead to one miracle drug, but rather to a wide spectrum of therapeutic options that have to be carefully matched to the specific patient.