[gdpawel]

Greg

Combination chemotherapy frequently, but not always, has produced greater degrees of clinical benefit than single agent therapy. There are two potential explanations for this. First, when two or more drugs are given, there is a greater probability that at least one of the drugs will be active. Second, there is the potential for true synergy, where the whole is greater than the sum of the parts.

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 cytometric 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.

Laboratory oncologists feel that conceptually, maintenance allows for a cytotoxic exposure when the cell enters a “chemosensitive” period in its life cycle. Cancer cells that are “out surviving” their normal counterparts often do so in a quiescent stage (G0 Gx). The GO phase is a period in the cell cycle in which cells exist in a quiescent state, where the cell is neither dividing nor preparing to divide.

In order to capture these cells, drugs must be present in the body when these cells awaken from their dormancy. As we have now achieved increasingly durable remissions in diseases like breast cancer, small cell lung and ovarian, we are confronting patients in long-term complete remission.

Regardless of all of this, most of the cells that leave home don't survive the journey in the blood or lymph systems and many cancerous cells that eventually do lodge in a distant organ simply remain dormant, leaving it up to the immune system to take care of them. Researchers have learned that full-blown metastasis is an extremely challenging trade and the great majority of cancer cells are not up to the task.

Even those malignant characters that manage to slither their way into the blood or lymph system usually fail to do anything further. Most tumor cells lack the streamlined form of the blood and immune cells that are designed for cross-body trafficking, shear forces in the smaller vessels may rip the intruders apart.

Hope you enjoyed your much needed vacation!

Greg