[gdpawel]

Good point Rich. Patients' patterns of sensitivity and resistance do not change in the absence of intervening chemotherapy. And even after a patient fails a previous chemotherapy treatment, the test still can be done once a patient waits at least four weeks. If proper protocol is followed, evaluability rates are very high. Greater than 95% of all specimens submitted produce clinically useful results.

Rather than mixing and matching approved drugs, assayists have used combinations designed to work in tandem to block cancer. Twenty years of work on the human genome has helped illuminate the intertwined mechanisms of cancer. Scientists are beginning to understand the cellular and genetic links among different disease pathways. As a result, the FDA is ready to allow innovative testing of drug cocktails.

Among the most sought after attributes of chemotherapy drug combinations is drug synergy. Synergy, defined as supra-additivity wherein the whole is greater than the sum of the parts, reflects an elegant interaction between drugs predicated on their modes of action. While some synergistic interactions can be predicted based upon the pharmacology of the agents, others are more obscure.

The application of synergy analyses may represent one of the most important applications of the functional profiling platform, enabling clinicians to explore both anticipated and unanticipated favorable interactions. Equally important may be the platform's capacity to study drug antagonism wherein two effective drugs counteract each others' benefits. This phenomenon, characterized by the whole being less than the sum of the parts, represents a major pitfall for clinical trialists who simply combine drugs because they can.

Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy. Patients benefit both in terms of response and survival from drugs and drug combinations found to be "active" in assays even after treatment failure with several other drugs, many of which are in the same class, and even with combinations of drugs found to have low or no activity as single agents but which are found in the assay to produce a synergistic and not merely an additive anti-tumor effect.

There would be a huge advantage to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug. As I stated before, 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.