Protein Kinase Inhibitors: Synthesis and Molecular Repurposing in Three-Dimensional Cancer Models PKI

The clinical challenges of treatment resistance and adverse reactions associated with targeted drug toxicity require significant expenditure on the development and trials of new therapeutic molecules. Such an approach as molecular repurposing allows "giving a second life" to available drugs by targeting them to new biotargets and testing them in various combinations. When developing new therapeutic strategies, it is important to consider the unique characteristics of different cancer tissues. Tumors of different organs may have different molecular profiles, and effective treatment should be directed exactly at targets specific to these tissues. This literature review is devoted to analyzing the current state of the pharmacological niche of protein kinase inhibitors, synthesis methods and the mechanism of action of existing approved drugs-inhibitors of major protein kinases. In addition, in this review we highlight modern approaches to modeling 3D tissue-specific organoids (tumoroids) used for testing anticancer agents, which are currently considered a promising platform for screening protein kinase inhibitors. Molecular drug repurposing and the next generation 3D organoids are important strategies in the fight against resistance to targeted drugs and in the development of new, more effective therapeutic agents.