The reason for the interest around the functional profiling test is that it allows the selection of the most effective and least toxic drug regimen for a cancer patient prior to initiating treatment. The use of this testing enables the patient’s treating physician to prescribe those agents with the highest probability of improving the patient’s outcome and minimizing unnecessary toxic therapies.
To understand more, Digital Journal spoke with cancer research pioneer and practicing oncologist, Dr. Robert Nagourney. Dr. Nagourney has worked for over twenty years refining a laboratory technique that measures how cancer cells respond when they are exposed to drugs and drug combinations.
Digital Journal: How has medical technology advanced in terms of cancer treatment?
Dr. Robert Nagourney: Slowly. The most important breakthrough being the first meaningful application of immuno-oncology. Beyond that, in highly select cases, so called “targeted drugs” are having an impact but cost, toxicity and the relative rapid development of resistance remain big issues.
DJ: How important is to select the appropriate drug for a particular cancer?
Nagourney: Highly critical. Modern oncology is practiced based upon an average patient model. That is, the drugs that work for the largest number of people, rarely a majority more often a plurality, are given to everyone! While the few who benefit do well, the remaining patients are not only not getting better , they may be getting worse, while other more active drugs aren’t being applied. It is very arguable that the wrong treatment is worse than no treatment at all.
DJ: How do you go about testing a patient’s cancer cells/tumors in your lab against potential cancer drugs?
Nagourney:We call it the Ex-Vivo Analysis of Programmed Cell Death (EVA-PCD) assay. This testing, also called functional profiling, exposes living cancer cells from individual patients to chemotherapy drugs, targeted agents and combinations.
The use of this testing enables the patient’s treating physician to prescribe those agents with the highest probability of improving the patient’s outcome and minimizing unnecessary toxic therapies.
To find the most effective treatment, living tumor cells from a patient are collected during biopsy or surgery. An analysis of this sample of the living cancer cells then shows which drugs kill the cancer cells (these cells are “sensitive” to these drugs) and which ones do NOT (these cancer cells are “resistant” to these drugs).
Living tumor cells are kept in clusters (microspheroids) that mimic the body’s environment. By examining cancer cells in their native state, to include cell-cell, cell-stromal (connective tissue), cell-vasculature (circulatory) and inflammatory processes, we take a snapshot of how they behave when exposed to various drugs, combinations and new targeted therapies.
These microspheroids reflect the complex elements of the body’s cellular environment which has proven critical for the accurate prediction of clinical response.
We isolate these 3-dimensional structures directly from each patient’s tumor to test drugs and combinations. It is because we capture cancer in its native state that our approach is the most accurate platform for response prediction.
With these results patient can be equipped with personalized information to make the most informed decision to treat their cancer.
By using therapies found active in the laboratory, we have been able to double response rates and improve survival for patients.
DJ: How long does this process take? What are the main challenges?
Nagourney:One week. The greatest challenge is to educate physicians upon the newest concepts of programmed cell death and the emerging field of cell phenoyopic studies. Doctors need to go beyond genomics to cellular biology, physiology and function.
DJ: Does this fit with the current focus on precision medicine?
Nagourney:In the current era, precision medicine has come to be defined as synonymous with genomic medicine. That is, to use gene profiles to identify targets and then treat with targeted drugs. But only a handful a patients reveal actionable mutations and those who do respond either briefly or not at all. Precision medicine as it used today is a misnomer. What patients want is effective medicine chosen rationally based upon tumor biology not based solely upon cell informatics. The reductionist thinking that led us to believe we could define the complexity of biology based upon DNA is rapidly proving wrong.
DJ: How successful has your approach been? Are there any case studies you can share?
Numerous published studies. In one meta-analysis of over 2500 peer-reviewed, published outcomes, patients who received “active” drugs selected in the laboratory had a 2.04 fold higher response rate ( P < 0.001) and a 1.44 fold higher one-year survival (p = 0.02). DJ: Is the medical world receptive to your approach?
Nagourney:Some are very receptive, some less so.
