Inappropriate modeling of chronic and complex disorders: How to reconsider the approach in the context of predictive, preventive and personalized medicine, and translational medicine

Abstract

Preclinical investigations such as animal modeling make the basis of clinical investigations and subsequently patient care. Predictive, preventive, and personalized medicine (PPPM) not only highlights a patient-tailored approach by choosing the right medication, the right dose at the right time point but it as well essentially requires early identification, by the means of complex and state-of-the-art technologies of unmanifested pathological processes in an individual, in order to deliver targeted prevention early enough to reverse manifestation of a pathology. Such an approach can be achieved by taking into account clinical, pathological, environmental, and psychosocial characteristics of the patients or an individual who has a suboptimal health condition. Inappropriate modeling of chronic and complex disorders, in this context, may diminish the predictive potential and slow down the development of PPPM and consequently modern healthcare. Therefore, it is the common goal of PPPM and translational medicine to find the solution for the problem we present in our review. Both, translational medicine and PPPM in parallel, essentially need accurate surrogates for misleading animal models. This study was therefore undertaken to provide shreds of evidence against the validity of animal models. Limitations of current animal models and drug development strategies based on animal modeling have been systematically discussed. Finally, a variety of potential surrogates have been suggested to change the unfavorable situation in medical research and consequently in healthcare.

Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target

“…Most targeted therapy drugs found therapeutically effective and safe in animal models failed in clinical trials due to toxic effects. 61 Compared with previous cancer metabolism studies that focused on either the glycolytic pathway or the lipid synthesis pathway, the feedback loop investigated in this study simultaneously regulates two biosynthetic metabolic pathways. In the context of translational medicine, the molecular target identified in this loop may offer better value for glioma treatment, as inhibitors at lower or tolerable doses may be sufficient to suppress tumor progression based on a combination of the inhibitory effects on both glycolysis and lipid synthesis.…”

“…Although therapies targeting tumor metabolic reprogramming can kill tumor cells, the associated toxic effects have restricted their application. Most targeted therapy drugs found therapeutically effective and safe in animal models failed in clinical trials due to toxic effects 61 . Compared with previous cancer metabolism studies that focused on either the glycolytic pathway or the lipid synthesis pathway, the feedback loop investigated in this study simultaneously regulates two biosynthetic metabolic pathways.…”

Pirfenidone: A novel hypothetical treatment for COVID-19

“…Nevertheless, a limited number of labs have access to animal models of COVID-19-SARS and can conduct experimental studies parallel or before human trials. We have no time to wait for animal modeling, and animal models do not necessarily provide valid shreds of evidence in this case in terms of toxicity or efficacy of treatments, because mortality of this virus is almost always due to interaction of the virus with human immune system and animals are not appropriate surrogate models here [67].…”

Commentary: Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused

“…We should model both the disease and the drug mechanism of action, irrelevant of their current application, and recommend novel treatments accordingly ( 3 , 4 ). Indeed, a large number of currently approved medications in medicine have been proposed for other totally irrelevant disorders; among them are Amantadine, Sildenafil, and Carbamazepine ( 5 ).…”