Larry Weisenthal, M.D., PhD.
The tumor holds the key to a patient's clinical outcome and survival. Each specimen must be individualized. Performing cell function analysis deserves the same degree of professional time and attention as major extirpative or debulking surgery or radiotherapy.
All sorts of specimens, from nice, sterile, viable sugar-cubed size pieces of tumor tissue from a sterile site to mucinous, contaminated low viability specimens from inside the colon lumen to several liters of bloody fluid to fried liver (from electrocautery biopsies of liver tumors) to small needle biopsies to bone marrow and blood specimens.
For solid tumors, testing is done with three-dimensional (3D) clusters (microclusters). It takes a lot of work to glean viable tumor cells and get a quantitative yield and separate tumor cells from normal and dead cells and get rid of mucin, and then to isolate the viable cell clusters from the discohesive, single cells and so on. Two specimens are seldom alike.
Not infrequently though, patients have a fairly major, invasive surgery primarily to get tumor for testing, so failure (an inevaluable assay) is not an option. Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy.
There would be a huge advantage to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug. The time and energy required to conduct an excisional biopsy pales in comparison to the time, energy and lost opportunities associated with months of ineffective, toxic therapy.
Reliable, sensitive and specific cell-death endpoints are needed in a functional cytometric profiling assay. At least three different cell-death endpoints are used for every specimen (of the five that are immediately at disposal). You've got to make sure that the signal that is being measured is really from tumor and not normal cells and different endpoints have different advantages and disadvantages, depending on the type of specimen.
In certain instances, one cell-death endpoint is biologically more valid than another. When you get the same result with multiple endpoints, there is confidence in the results. When there is disagreement, and there is no readily understandable reason for the disagreement, much more caution is done in using this information for treatment recommendations.
Functional cytometric profiling is not a simple, turn-key solution. It is more a professional service, more than a simple laboratory test. It is sometimes thought of as a practicing the specialty of "Laboratory Oncology." I am an early member of an emerging new medical specialty, which I refer to as Laboratory Oncology. The function of the laboratory oncologist is to utilize available forms of laboratory testing of tumor biopsies to best individualize (personalize) cancer treatment with drugs, radiation, and/or surgery.
These forms of laboratory testing are based on multiple approaches, including traditional anatomic pathology, molecular genetics, and cell biology (typically through the application of cell culture methodologies). The importance of Laboratory Oncology is that there is an exploding growth in the number of anti-cancer drugs, which tend to be of only partial and unpredictable efficacy, which are often toxic, and which are extremely expensive. There is a huge need for existing and improved methodologies to best match treatment to the patient.
Dr. Weisenthal is Medical and Laboratory Director, Weisenthal Cancer Group, Huntington Beach, California
Dr. Weisenthal thinks that one day there will be residencies for subspecialty training in Laboratory Oncology. Doing it properly requires either an M.D./PhD oncologist with at least a street education in pathology or else a collaboration between an oncologist, pathologist and PhD cell biologist.