Sometimes the genetic signal may not be the driver mutation. Other signaling pathways, like passenger mutations, could be operative.
Driver mutations are the ones that cause cancer cells to grow, whereas passengers are co-travellers that make no contribution to cancer development. It turns out that most mutations in cancers are passengers.
However, buried among them are much larger numbers of driver mutations than was previously anticipated. This suggests that many more genes contribute to cancer development than was thought.
Cells speak to each other and the messaages they send are interpreted via these intracellular pathways. You wouldn't know this using analyte-based genomic and proteomic methodologies. However, functional phenotype analysis provides the window. It can test various cell-death signaling pathways 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.
The functional cytometric profiling platform has the capacity to measure genetic and epigenetic events as a functional, real-time adjunct to static genomic and proteomic platforms.
As virtually every presentation at the 2012 American Association for Cancer Research (AACR) meeting made obligatory reference to genomic analysis, almost every one of them then doubled back to metabolism as the principal driver of human cancer.
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.
Gene Mutation vs Chromosomal Theory of Cancer
http://cancerfocus.org/forum/showthread.php?t=3764
Driver Mutations and Passenger Mutations on the road to cancer
http://cancerfocus.org/forum/showthread.php?t=3808