New Molecule Targets Proteins Inside Cancer Cells.

A paper on WT1 prognosis in breast cancer

http://www.ncbi.nlm.nih.gov/pubmed/22797561

I saw this topic and thought immediately, "OMG...wait til ihatesnow sees this! " And now I see she already did...LOL!

There are different types of targeted therapies, defined in three broad categories.

First. There are a variety of target receptors that are on the outside or surface of the cell. This form of targeted treatment includes the monoclonal antibodies.

Second. Some targeted therapies focus on the internal components and function of the cancer cell. These use small molecules that can get into the cell and disrupt the function of the cells, causing them to die. 

Third. Antiangiogenesis inhibitors target the blood vessels that supply oxygen to the cancer cells, ultimately causing the cells to starve and die.

It may be very important to zero in on different proteins. However, when actually taking the "targeted" drug, will it even enter the cancer cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? In other words, will it work for every individual patient that used the drug?

Simply having a target (even inside the cell) doesn't ensure that the drug will work. The drug might not get inside the cell at all. The drug can get pumped out of the cell. The drug can be inactivated by the cell. The cell can recover from the damage called by the drug by repairing damage or shutting down the cell death pathway or whatever.

All the validations of this protein or that protein provides us with a variety of sophisticated techniques to provide new insights into the tumorigenic process, but if the "targeted" drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, it just isn't going to work.

Metabolism is the principal driver of human cancer. Cells speak to each other and the messages they send are interpreted via intracellular and intercellular pathways. You wouldn't know this using analyte-based proteomic methodologies. However, functional phenotype analysis can provide the window by testing various cell-death signaling pathways upstream and downstream.

While most scientists use genomic or proteomic platforms to detect mutations in these pathways that might result in response to chemicals, functional cytometric platforms have taken a different tack. By applying functional analysis, to measure the end result of pathway activation or deactivation, they can predict whether patients will actually respond.