Cancer gene testing service launched by Lab21
January 25th, 2008
‘Being able to select which patients are more likely to respond to therapy is an important step forward in the treatment of cancer’.
For example, scientists have shown recently that cetuximab, a new treatment for colorectal cancer, is poorly responsive if the tumours carry a mutated K-ras gene.
Similarly, mutations in K-ras also confer resistance to erlotinib, a small molecule treatment for lung cancer.
At 6:23 pm on June 17th, 2008 Gregory D. Pawelski said:
Identifying Clinical Responders
Drug companies are betting on the future of targeted medicine, hoping to improve patient outcomes by using genetic tests to figure out which patients could benefit from a given drug. The pressure is so great that companion molecular diagnostics approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.
If you find one or more implicated genes in a patient’s tumor cells, how do you know if they are functional (is the encoded protein actually produced)? If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell?
All cells exist in a state of dynamic tension in which several internal and external forces work with and against each other. Just detecting an amplified or deleted gene won’t tell you anything about protein interactions. Are you sure that you’ve identified every single gene that might influence sensitivity or resistance to a certain class of drug?
Assuming you resolve all of the preceeding issues, you’ll never be able to distinguish between susceptibility of the cell to different drugs in the same class. Nor can you tell anything about susceptibility to drug combinations. And what about external facts such as drug uptake into the cell? You’re not going to accomplish this using genetic tests!
The “cell” is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems’ response to drug treatments, not just one or a few targets or pathways.
Cell-based functional profiling 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 function, hence all the different pathways/mechanisms which correlate in different situations. Improvement can be made by measuring what happens at the end of all processes, rather than the status of the individual pathways/mechanisms. You still need to measure the net effect of all processes, not just the individual molecular ‘targets.’