Abstract
The fundamental pathophysiology of malignancies is dysregulation of the signalling pathways. 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 atypical 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 tumours, 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 cancers. However, there are still groups of patients who have a poor prognosis, where the intensification 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 hopefully 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.
Highlights
In recent years, we have observed tremendous progress in paediatric haemato-oncology [1]
The results of the study by the Children’s Oncology Group (COG) and the European Study of Postinduction Treatment of Ph-Positive acute lymphoblastic leukaemia (ALL) (EsPhALL) consortium suggested that the combination of chemotherapy and tyrosine kinase inhibitors (TKIs), without Haematopoietic stem cell transplantation (HSCT) in the first remission (CR1), could be an effective treatment approach for Ph+ ALL paediatric patients
Twenty years have passed since the approval of the first TKI, which started the target therapy era
Summary
We have observed tremendous progress in paediatric haemato-oncology [1]. In view of the small target group and the ethical complexities of drug testing in children, paediatric patients are often forgotten in clinical. 2021, 22, 12089 molecular science and an understanding of genetic predispositions to tumour formation have produced a new treatment option called target therapy, which influences the activity of specific enzymes that are involved in carcinogenesis. Sci. 2021, 22, 12089 molecular science and an understanding of genetic predispositions to tumour formation have produced a new treatment option called target therapy, which influences the activity of specific enzymes that are involved in carcinogenesis This approach reduces the toxicity of the therapy but is more specific to tumour cells and has already led to beneficial clinical effects [18]
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