From Bench to Bedside: Does Preclinical Practice in Translational Oncology Need Some Rebuilding?

Abstract

"After years of enormous research efforts for the systematic cataloguing of genetic alterations with causative function in cancer, the goal of “personalized medicine” in clinical oncology is now potentially in reach (1). With the overall aim to characterize more than 25,000 genomes from the 50 more relevant cancer types, major international endeavors are ongoing to provide a complete inventory of oncogenic mutations (2). When combined with the massive capacity of modern pharmaceutical companies to screen for inhibitors that target “druggable” mutant gene products, this undertaking will offer unprecedented opportunities to treat cancer through “precision” approaches whereby therapeutic decisions are informed by the genomic makeup of each tumor in each patient.

Nevertheless, the ultimate clinical implementation of personalized medicine in oncology is still a major challenge. Indeed, the categorization of molecularly circumscribed tumor subpopulations featuring specific genetic lesions, the validation of such lesions as therapeutic targets, and the definition of biomarkers for accurate prediction of sensitivity to rational treatments face technical, logistic, and ethical limitations in patients. If cancer therapies must be tailored around small, genetically defined patient subgroups, the efforts essential to identify, recruit, and treat a number of patients great enough to validate the therapeutic relevance of new targets must be massive and may hardly justify high-risk drug development strategies. Highly reliable preclinical models for discrimination between “actionable” therapeutic opportunities and those with weak clinical transferability are thus urgently needed to improve the bench-to-bedside … 

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