This is a perfect example that it would be more advantageous to sort out what's the best "profile" in terms of which patients benefit from this drug or that drug. Can they be combined? What's the proper way to work with all the new drugs? If a drug works extremely well for a certain percentage of cancer patients, identify which ones and "personalize" their treatment. If one drug or another is working for some patients then obviously there are others who would also benefit. But, what's good for the group (population studies) may not be good for the individual.
Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival above that achieved with "best guess" empiric chemotherapy through clinical trials.
Gene expression means, is RNA being made from the gene. So gene expression assays can be either probing for the specific RNA messengers (messenger RNA) or it can mean looking for the proteins themselves. Like testing cancer for the presence of receptors and over-expression of growth factor receptors. However, most drugs cannot be looked at in this way and tests that are now in use have limited predictive accuracy.
It may be very important to zero in on different genes and proteins. However, when actually taking the "targeted" drugs, do the drugs 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 patient?
All the validations of this gene 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.
To overcome the problems of heterogeneity in cancer and prevent rapid cellular adaptation, oncologists are able to tailor chemotherapy in individual patients. This can be done by testing "live" tumor cells to see if they are susceptible to particular drugs, before giving them to the patient. DNA microarray work will prove to be highly complementary to the parellel breakthrough efforts in targeted therapy through cell function analysis.
Dr. Ronald DePinho, director of the Center for Applied Cancer Science at the Dana-Farber Cancer Institute and lead researcher of this study, argues for quick movement to clinical trials "that combine three or more such targeted drugs for such cancers to shut down all the malfunctioning growth switches."
Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, in a response about the Cancer Genome Project, said "We're going to be able to take a cancer specimen, analyze it, and follow those genetic changes that influence particular pathways, then we'll use one, two, three of more "targeted" therapies, perhaps simultaneously, and be able to completely interrupt the flow of the cancer process."
Dr. Arny Glazier, cancer researcher in his book, "Cure: Scientific, Social and Organizational Requirements for the Specific Cure of Cancer," the consistent and specific cure or control of cancer will require multiple drugs administered in combination targeted to abnormal patterns of normal cellular machinery that effect or reflect malignant behavior. It means finding the patterns of malignant cells and develop a set of five to ten drugs in order to cure or control cancer.
I agree! Upgrading clinical therapy by using drug sensitivity assays measuring "cell death" of three dimensional microclusters of "live" fresh tumor cell, can improve the situation by allowing more drugs to be considered. The more drug types there are in the selective arsenal, the more likely the system is to prove beneficial.
As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate new medicines and treatments for cancer. More emphasis should be put on matching treatment to the patient, through the use of individualized pre-testing.
EGFRx™ Targeted Therapy Profile
http://weisenthalcancer.com/Patient%...RXPatients.htm