Matching Tumors to Drugs
It is critical that those receiving a drug matched to their tumor fare better than is typically seen with standard chemotherapy. So many cancer patients are chasing mets because the first-line standard therapy did not work. But what happens when there are too many receptors (pathways/mechanisms) and the cancer still continues to grow and divide?
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.
Cancer cells have many mutations in many different pathways, so even if one route or two is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeted drugs have not been accompanied by reliable, specific predictive tests allowing for rational and economical use of these drugs. Molecular diagnostics (genetic profiles) approved often have been mostly or totally ineffective at identifying clinical responders to the various therapies.
Gene profile testing examines a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predispostion to drug response.
Gene profile testing involves the use of dead, formaldehyde preserved cells that are never exposed to 'targeted' drugs. Gene profile 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.
Gene profile 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 Gene profile tests tell us anything about drug combinations.
If you find one or more implicated genes in a patientís 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?
Are you sure that youíve identified every single protein that might influence sensitivity or resistance to these drugs? 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.
There are many mechanisms/pathways to altered cellular function. Functional profiling measures what happens at the end, rather than the status of the individual mechanisms/pathways. Cancer is a complex disease and needs to be attacked on many fronts.