The use of inhibitors of tyrosine kinase in paediatric haemato‐oncology—when and why?

Abstract

The fundamental pathophysiology of malignancies is dysregulation of the signalling path-ways. Protein tyrosine kinases (PTKs) are among the enzymes which, if mutated, play a critical role in carcinogenesis. The best‐studied rearrangement, which enhances PTK activity and causes atypi-cal proliferation, is BCR‐ABL1. Abnormal expression of PTKs has proven to play a significant role in the development of various malignancies, such as chronic myelogenous leukaemia, brain tu-mours, neuroblastoma, and gastrointestinal stromal tumours. The use of tyrosine kinase inhibitors (TKIs) is an outstanding example of successful target therapy. TKIs have been effectively applied in the adult oncology setting, but there is a need to establish TKIs’ importance in paediatric patients. Many years of research have allowed a significant improvement in the outcome of childhood can-cers. However, there are still groups of patients who have a poor prognosis, where the intensifica-tion of chemotherapy could even cause death. TKIs are designed to target specific PTKs, which lead to the limitation of severe adverse effects and increase overall survival. These advances will hope-fully allow new therapeutic approaches in paediatric haemato‐oncology to emerge. In this review, we present an analysis of the current data on tyrosine kinase inhibitors in childhood cancers.