I'm posting here the Introduction. The full book is available on Amazon at $64.00 and perhaps represents the best Christmas gift ever and a must for your library (if you are my mother). Otherwise, if you are just curious to see how evolution tools (i.e., taxonomy) can be oddly applied to drug classification, have a try.
In spite of the progress of modern biological research, the wealth of novel findings on human physio-pathology and the adoption of ‘omic tools’, the number of novel drugs is not increasing. On the contrary, the attrition rate in drug discovery is constantly rising. The cause of this is object of a major debate; certainly a current major limitation in drug discovery and development is the assessment of drug efficacy.
A drug therapy is efficacious when it evokes the desired biological effect. Biological effects could be physiological phenomena (i.e., muscular contraction) or molecular events (i.e., increased expression of a target gene) and usually this effect responds to drug treatment in a dose-dependent manner. Today, because of our better understanding of the complexity of the cellular biology, the assessment of efficacy in ‘molecular terms’ (useful for drug development purposes) becomes of difficult application. Most of the drugs act by binding to a cellular receptor: upon binding, drugs ‘activate’ the receptor, initiating the signaling cascade responsible for the biological effect; we know that a single drug can induce different signaling cascades, and this ability may change significantly with respect to a spatial constraint, the tissue where the drug is acting, and to a temporal constraint, the timeline over drug administration. In short, a candidate drug designed to stimulate a particular biological process, could, as expected, behave as agonist in the first week of therapy and suddenly turns to an antagonist profile (with comprehensible deleterious side effects). Likely, such a candidate drug would be discarded in the drug development pipeline: in fact, it is common for unforeseen toxic profiles to be discovered late in the pipeline, already at the level of clinical studies in humans. This is unwanted: a failure of a clinical trial is a great loss for a pharmaceutical company and, ultimately, a missed opportunity for the whole healthcare sector. A comprehensive knowledge of drug actions in space and time is pivotal for the assessment of drug efficacy; unfortunately, this is accomplished only during clinical studies.
This book discusses a concept...