As the clinical use of biologic response modifiers continues to increase, the old way of estimating effective doses in oncology, i.e. reaching dose-limiting toxicities, is becoming obsolete. Biologic response modifiers and targeted therapies are less toxic and their effective dose is often left shifted on the dose response curve. This is why the majority of pharmaceutical companies have opened new programs seeking biomarker of therapeutic response, and why numerous research programs have been announcing Request for Applications in order to find and evaluate biomarkers of disease.
Because of the ease of procurement of the clinical specimen, plasma and serum, remain the favorite clinical analytes. However, the sheer numbers of different plasma proteins, the many thousand fold differences in the amounts of the potential protein biomarkers, and the lack of specificity of plasma proteins have hindered the search. The ability to detect changes in the levels of proteins expressed in picomolar quantities are mired by the presence of more abundant nonspecific proteins such as albumin or immunoglobulins. Most meaningful changes, those that occur in the amounts of free proteins, remain very difficult to evaluate.
The recent discovery that angiogenesis regulators are actively and selectively sequestered in platelets early in cancer, has led to renewed hopes of finding circulating biomarkers that would help in early disease detection, and improve our ability to detect an early therapeutic response. There are early indicators that this is the case in other diseases as well, and that the focus may be shifting from analyzing plasma and serum, to analyzing platelets.