[gdpawel]

Amy

Targeted drugs are specifically designed to block one or more critical pathways involved in cancer-cell growth and metastases. The development of these therapies stems from advances in molecular biology that have permitted the identification of qualitative and quantitative differences in gene expression between cancer cells and normal cells.

However, there are lots of things which determine if drugs work, beyond the existence of a given "target." Does the drug even get into the cancer cell? Does it get pumped out of the cell? Does the cell have ways of escaping drug effects? Can cells repair damage caused by the drug? Do combinations of drugs work in ways which can't be predicted on the basis of static gene expression patterns?

Tumor biology is a lot more complex than we'd like it to be. Cancer is more complex than its gene signature. Many common forms of cancer present as a host of mutated cells, each with a host of mutations. And they're genetically unstable, constantly changing. That's why so many cancers relapse after initially successful treatment. You kill off the tumor cells that can be killed off, but that may just give the ones that are left a free reign.

The idea of searching for clinical responders by testing for a single gene mutation seems nice, but as we've seen with Herceptin, you may have to test for dozens of protein expressions that may be involved in determining sensitivity/resistance to a given drug. Because if you miss just one, that might be the one which continues cancer growth.

Human beings are demonstrably more than the sum of their genes. Cancer biology and the study of cancer therapy are many things, but simple is not one of them. Complex problems require solutions that incorporate all of their complexities, however uncomfortable this may be for genomic investigators.

Greg