Title : Glioblastoma treatment: Small molecule Tyrosine Kinase Inhibitors (TKIs)
Abstract:
Over the past ten years, numerous small molecules, typically featuring heterocyclic frameworks, have been developed and synthesized as inhibitors of tyrosine kinases (TKIs). Among these, several compounds have undergone evaluation at both preclinical and clinical stages for the treatment of glioblastoma multiforme (GBM). GBM is recognized as the most prevalent and aggressive form of brain cancer, characterized by a poor prognosis, with a median survival time of 15 to 16 months and a five-year survival rate of merely 5%. Despite recent progress in GBM therapies, it remains an incurable condition marked by treatment resistance and high rates of recurrence. Consequently, there is a pressing need for the creation of novel pharmacological agents to combat this malignancy. This review presents compounds published in the last five years that have demonstrated promising efficacy in preclinical models of GBM as TKIs. The compounds are categorized according to the specific kinases they target: initially, receptor TKIs were discussed, followed by inhibitors of cytoplasmic and unique kinases. For each small molecule, the chemical structure was provided and the interaction with the target for select representative compounds was illustrated, in order to clarify their mechanisms of action. Lastly, the most significant clinical trials related to these compounds were referenced.
