[gdpawel]

Targeted therapies are typically not very effective when used singularly or even in combination with conventional chemotherapies. The targets of many of these drugs are so narrow that cancer cells are likely to eventually find ways to bypass them. Durable responses are rare and no one with advanced cancer has yet to be cured with targeted therapy. Physicians may have to combine several targeted treatments to try an achieve cures or durable responses.

So, some clinical studies are trying to delineate the benefit achieved when combining two innovative targeted treatments together. However, these targeted therapies produce limited results because they can help a relatively small subgroup of cancer patients, and tests to pinpoint those patients are desperately needed. The trick is figuring out which patients will respond. The challenge is to figure out which patients to give them to. There is a targeted assay to match targeted cancer therapies to those cancer patients.

The targeted assay uses "whole cell profiling" which is a variety of metabolic (cell metabolism) and morphologic (structure) measurements to determine if a specific drug is successful at killing the patient's cancer cells. Whole cell profiling measures genes before and after drug exposure. It makes the statistically significant association between prospectively reported test results and patient survival.

And it is the only cell-death endpoint assay system in which drug effect upon cancer cells is visualized directly. Photomicrographs of actual tumor cells show the condition of cells as they are received and enriched in the lab, and also the conditions of control cells post-culture. In this visualization, the microscopic slides sometime show that the exact same identical individual culture well, shows some clusters have taken up vast amounts of the molecular drug, while right next door, clusters of the same size, same appearance, same everything haven't taken up any of the drug.

It doesn't matter though if there is a target molecule (protein or receptor) in the cell that the targeted drug is going after. If the 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, drug resistance is multifactorial. The one advantage of whole cell profiling is that it can show this at the cell "population" level, measuring the interaction of the entire genome.

This could help solve the problem of knowing which patients can benefit from these molecular drugs. Afterall, these "smart" drugs do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

Literature Citation: Weisenthal, LM, Patel, N, and Rueff-Weisenthal, C. Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood. J Intern Med 264:275-287, September 2008