[gdpawel]

Targeted therapy is designed to block a specific gene or protein that has a critical role in the survival, growth, invasion, or metatasis of a specific cancer cell. It takes advantage of the biologic differences between cancer cells and healthy cells by 'targeting' faulty genes or proteins that contribute to the growth and development of cancer.

In other words, 'targeted' treatments fight cancer by correcting or modifying defective 'pathways' in a cancer cell. In healthy cells, each 'pathway' is tightly controlled. For instance, healthy cells are allowed to divide into new cells, and damaged cells are destroyed. However, in cancerous cells, certain points in the 'pathway' become disrupted, usually through a genetic mutation (change in form).

Designing "targeted" anticancer drugs begins with identifying the genes or proteins that are specific to the development of cancer and testing whether blocking those genes or proteins gets rid of the cancer. Genetic (molecular) tests are instrumental in accomplishing this task.

However, understanding 'targeted' treatments begins with understanding the cancer cell. Every tissue and organ in the body is made of cells. In order for cells to grow, divide, or die, they send and receive chemical messages. These messages are transmitted along specific 'pathways' that involve various genes and proteins in a cell.

Genetic-based testing examines a single process within the cell or a relatively small number of process. The aim is to tell if there is a theoretical predispostion to drug response. Cell-based testing not only examines for the presence of genes and proteins but also for their 'functionality' (their interaction with other genes, proteins, and processes occurring within the cell, and for their response to 'targeted' drugs).

Genetic-based testing involves the use of dead, formaldehyde preserved cells that are never exposed to 'targeted' drugs. Genetic-based tests cannot tells us anything about uptake of a certain drug into the cell or if the drug will be excluded before it can act or what changes will take place within the cell if the drug successfully enters the cell.

Genetic-based tests cannot discriminate among the activities of different drugs within the same class. Instead, it assumes that all drugs within a class will produce precisely the same effect, even though from clinical experience, this is not the case. Nor can Genetic-based tests tell us anything about drug combinations.

Cell-based testing looks at 'fresh' living cancer cells. It assesses the net result of all cellular processes, including interactions, occurring in real time when cancer cells actually are exposed to specific anti-cancer drugs. It can discriminate differing anti-tumor effects of different drugs within the same class. It can also identify synergies in drug combinations.

When considering a 'targeted' cancer drug which is believed to act only upon cancer cells that have a specific genetic defect, it is useful to know if a patient's cancer cells do or do not have precisely that defect. Although presence of a 'targeted' defect does not necessarily mean that a drug will be effective, absence of the targeted defect may rule out use of the drug.

As you can see, just selecting the right test to perform in the right situation is a very important step on the road to personalizing cancer therapy. Sometimes a drug will inhibit the 'target' but not stop the growth of cancer. Not all genes and proteins have a critical role in the survival and growth of cancer cells.

The are many pathways to altered cellular (forest) function, hence all the different 'trees' which correlate in different situations. Improvement can be made by measuring what happens at the end of all processes (the effects on the forest), rather than the status of the individual trees (pathways/mechanisms). You still need to measure the net effect of all processes, not just the individual molecular (gene/protein) targets.