Breast Cancer Genetic Profiling Has Not Achieved Personalized Medicine Yet

[gdpawel]

In the first head-to-head clinical trial comparing gene expression patterns with Personalized Cancer Cytometric testing (also known as “functional tumor cell profiling” or “chemosensitivity testing”), Personalized Cancer Cytometrics was found to be substantially more accurate.

In a clinical trial involving ovarian cancer patients, patterns of gene expression identified through molecular gene testing were compared with results of Personalized Cancer Cytometric testing (in which whole, living cancer cells are exposed to candidate chemotherapyterm drugs). Four different genes were included in the molecular part of the study. The four genes were selected as those which researchers believe to have the greatest likelihood of accurately predicting individual patient response to specific anti-cancer drugs.

Study Results:

For two of the genes studied, there was no significant correlation between gene expression pattern and patient response. In other words, results for these genes were found to be meaningless. For the third gene studied, there was a 75% correlation between expression and patient response. This means that the gene was 75% accurate when it came to identifying an active drug for that patient. For the fourth gene studied, the accuracy in identifying an active drug was only 25%. In marked contrast, Personalized Cancer Cytometric testing was found by the researchers to be 90% accurate in identifying active drugs for ovarian cancer patients in this study.

Discussion:

Molecular testing – that is, testing for gene expression patterns – is widely studied and heavily promoted as a method to identify effective chemotherapy drugs for individual cancer patients. However, most studies of molecular testing carried-out to date show only modest correlation or no correlation between test results and actual patient response. In other words, much work remains to be done before molecular gene testing can be regarded as an accurate tool for chemotherapy selection. And yet in this, first ever, head-to-head study of test accuracy, Personalized Cancer Cytometrics was found to be highly accurate when it came to identifying effective drugs.

Comparing this study with previous studies:

Although this was the first head-to-head trial, the accuracy levels found in this trial for Personalized Cancer Cytometric testing are strikingly consistent with those documented in dozens of previous studies, published by respected cancer researchers around the world. In those studies, as in this one, extremely high levels of correlation (in other words, high levels of test accuracy) were found for Personalized Cancer Cytometrics.

Arienti et al. Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy. Journal of Translational Medicine 2011, 9:94.

http://www.translational-medicine.com/content/9/1/94

[gdpawel]

The genomic profile is so complicated, with one thing affecting another, that it isn't sufficient and not currently useful in selecting drugs. Because metabolic changes are complex and hard to predict, metabolic profiling will be essential for selecting best treatment.

In drug selection, molecular (genomic) 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 predisposition to drug response. It attempts to link surrogate gene expression to a theoretical potential for drug activity.

It relies upon a handful of gene patterns which are thought to imply a potential for drug susceptibility. In other words, molecular testing tells us whether or not the cancer cells are potentially susceptible to a mechanism/pathway of attack.

It doesn't tell you if one targeted drug (or combination of targeted drugs) is better or worse than another targeted drug (or combination) which may target a certain or a small number of mechanisms/pathways.

Functional profile testing doesn't dismiss DNA testing, it uses all the information, both genomic and functional, to design the best targeted treatment for each individual, not populations. It tests for a lot more than just a few mutations.

Functional profiling consists of a combination of a (cell morphology) morphologic endpoint and one or more (cell metabolism) metabolic endpoints. It studies cells in small clusters or micro-spheroids (micro-clusters). The combination of measuring morphologic and metabolic effects at the whole cell level.

The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. One needs to analyze the systems' response to targeted drug treatments, not just a few targets (pathways).

http://www.medicalnewstoday.com/releases/241306.php