Frustrating Reality – When a Tumor Sample is Insufficient for Testing
Updated: Oct 24, 2021
The principles underlying the Rational Therapeutics EVA-PCD platform reflect many years of development. Recognizing the importance of cell death measures — apoptotic and non-apoptotic — our laboratory dismissed growth-based assays. The closure of Oncotech, the principal purveyor of proliferation-based assays, illustrates the demise of a failed paradigm in the study and testing of human tumor biology. A second principal of our work is the need to examine all of the operative mechanisms of cell death (autophagic, necrotic, etc.). Laboratories that measure only one mechanism of cell death (e.g. caspase activation as a measure of apoptosis) miss important cell responses that are critical to the accurate prediction of clinical response. The third principle of our work is the maintenance of cells in their native state.
These fundamentals provide the basis of our many successes, but also a constraint. Because we do not propagate, subculture or expand tissues, we can only work with the amounts of tissue provided to us by our surgeons. While some labs propagate small biopsy samples into larger populations by growth to confluence, this introduces irreconcilable artifacts, which diminish the quality of sensitivity profiles. Avoiding this pitfall, however, demands that a tissue sample be large enough (typically 1cm3) to provide an adequate number of cells for study without growth or propagation.
This is the reason our laboratory must request biopsies of adequate size. The old computer dictum of “garbage in, garbage out” is doubly true for small tissue samples. Those that contain too few tumor cells, are contaminated, fibrotic or inadequately processed will not serve the patients who are so desperately in need of therapy selection guidance. As a medical oncologist, I am deeply disappointed by every failed assay and I am more familiar than most with the implications of a patient requiring treatment predicated on little more than intuition or randomization. We do everything within our power to provide results to our patients. This sometimes requires low yield samples be repeatedly processed. It may also set limitations on the size of the study or, in some circumstances, forces us to report a “no go” (characterized as an assay with insufficient cells or insufficient viability). Of course, it goes without saying that we would never charge a patient for a “no-go” assay beyond a minimal set up fee (if applicable). But, more to the point, we suffer the loss of an opportunity to aid a patient in need. Cancer patients never undergo therapy without a tissue biopsy. Many have large-volume disease at presentation, so it is virtually always possible to obtain tissue for study if a dedicated team of physicians makes the effort to get it processed and submitted to our laboratory. 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.