Why Doesn’t Rational Therapeutics do Gene Mutation Analyses?

Many patients inquire why we as a laboratory have not focused upon genomic analyses as part of the services we offer. There are several reasons why we have not focused on genomics. The first reason is that there are many laboratories that already commercially offer these analyses. These gene array methods can be automated and conducted comparatively cheaply. As we work hand-in-hand with many of the commercial purveyors of these techniques, we have seen little advantage in reproducing these methodologies in our facilities.

The second and more important reason that we have not pursued genomics reflects our belief that cancer is more complex than its gene signature. This point is critical to an understanding of what functional analyses are. We know that contained within the genes of each human is the information to create every protein, every enzyme, every lipid, every carbohydrate and all the organs and systems dependant upon their function. What we don’t know is how all of those 25,000+ genes are regulated to produce the unique features that constitute us as human entities.

From the moment of conception, when the male and female genetic materials are fused into what is known as a zygote, our informatics are established. What enables that single cell to become the multi-trillion-cell organism that we recognize as human is not the gene, but the gene regulation.

The informatics are static — the regulation, highly fluid.

Simply exploring the information contained within the human cell provides you with a blueprint of what may be, but no clear evidence that the outline structure will ever come to be in all of its functional complexity. In this regard, genomic analyses cannot approximate the vagaries and manifold variations that define us as individuals.

To look at this a different way, we can describe genetic information as “permissive, ” that is it tells you what you may or may not become. Functional information is “predictive,” it tells you exactly what you are. We have moved away from genomic analyses for the very reason that they provide only a veneer of information. The substance of cancer, its responsiveness to therapeutics and its ultimate cure, require a more definitive analysis. By studying human cellular behavior within the context of vascular, stromal and inflammatory elements, the EVA-PCD platform provides the closest approximation of human biology possible short of a clinical trial.

Human beings are demonstrably more than the sum of their genes. Cancer biology and the study of cancer therapy are many things, but simple is not one of them. Complex problems require solutions that incorporate all of their complexities, however uncomfortable this may be for genomic investigators.

National Cancer Institute Stops Gene-based Clinical Trials – Part 2

Last week we discussed the National Cancer Institute’s suspension of three ongoing clinical trails using genomic platforms to select therapies for cancer patients. This week, we seek to answer the question: What went wrong?

The simple answer is that cancer isn’t simple.

Cancer dynamics are not linear. Cancer biology does not conform to the dictates of molecular biologists. Once again, we are forced to confront the realization that genotype does not equal phenotype.

In a nutshell, cancer cells utilize cross talk and redundancy to circumvent therapies. They back up, zig-zag and move in reverse, regardless of what the sign posts say. Using genomic signatures to predict response is like saying that Dr. Seuss and Shakespeare are truly the same because they use the same words. The building blocks of human biology are carefully construed into the complexities that we recognize as human beings. However appealing gene profiling may appear to those engaged in this field (such as Response Genetics, Caris, the group from Duke and many others) it will be years, perhaps decades, before these profiles can approximate the vagaries of human cancer.

Functional analyses like the EVA-PCD platform, which measure biological signals rather than DNA indicators, will continue to provide clinically validated information and play an important role in cancer drug selection. The data that support functional analyses is demonstrably greater and more compelling than any data currently generated from DNA analyses.