|
Cell Lines vs Fresh Cells and Combination Therapy
Cell-lines have always played and continue to play an important role in drug screening and drug development.
The problem is that cell-lines do not predict for disease or patient specific drug effects. If you can kill breast cancer cell-lines with a given drug (or combination), it doesn't tell you anything about how the drug will work in real world, clinical breast cancer (real-world conditions). But you can learn certain things about general drug biology through the study of cell-lines.
As a general rule, studies from established cell-lines (tumor cells that are cultured and manipulated so that they continue to divide) have proved worthless as models to predict the activity of drugs in cancer. They are more misleading than helpful. An established cell-line is not reflective of the behavior of the fresh tumor samples (live samples derived from tumors) in primary culture, much less in the patient.
Established cell-lines have been a huge disappointment over the decades, with respect to their ability to correctly model the disease-specific activity of new drugs. What works in cell-lines do not often translate into human beings. You get different results when you test passaged cells compared to primary, fresh tumor.
Research on cell-lines is cheap compared to clinical trials on humans. But one gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissue.
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.
|
Linear Mode
