In the last few years, small molecules endowed with different heterocyclic scaffolds have been developed as kinase inhibitors. Some of them are being tested at preclinical or clinical levels for the potential treatment of neuroblastoma (NB). This disease is the most common extracranial solid tumor in childhood and is responsible for 10% to 15% of pediatric cancer deaths. Despite the availability of some treatments, including the use of very toxic cytotoxic chemotherapeutic agents, high-risk (HR)-NB patients still have a poor prognosis and a survival rate below 50%. For these reasons, new pharmacological options are urgently needed. This review focuses on synthetic heterocyclic compounds published in the last five years, which showed at least some activity on this severe disease and act as kinase inhibitors. The specific mechanism of action, selectivity, and biological activity of these drug candidates are described, when established. Moreover, the most remarkable clinical trials are reported. Importantly, kinase inhibitors approved for other diseases have shown to be active and endowed with lower toxicity compared to conventional cytotoxic agents. The data collected in this article can be particularly useful for the researchers working in this area.

Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma

D'Agostino, Ilaria;
2021-01-01

Abstract

In the last few years, small molecules endowed with different heterocyclic scaffolds have been developed as kinase inhibitors. Some of them are being tested at preclinical or clinical levels for the potential treatment of neuroblastoma (NB). This disease is the most common extracranial solid tumor in childhood and is responsible for 10% to 15% of pediatric cancer deaths. Despite the availability of some treatments, including the use of very toxic cytotoxic chemotherapeutic agents, high-risk (HR)-NB patients still have a poor prognosis and a survival rate below 50%. For these reasons, new pharmacological options are urgently needed. This review focuses on synthetic heterocyclic compounds published in the last five years, which showed at least some activity on this severe disease and act as kinase inhibitors. The specific mechanism of action, selectivity, and biological activity of these drug candidates are described, when established. Moreover, the most remarkable clinical trials are reported. Importantly, kinase inhibitors approved for other diseases have shown to be active and endowed with lower toxicity compared to conventional cytotoxic agents. The data collected in this article can be particularly useful for the researchers working in this area.
2021
Musumeci, Francesca; Cianciusi, Annarita; D'Agostino, Ilaria; Grossi, Giancarlo; Carbone, Anna; Schenone, Silvia
File in questo prodotto:
File Dimensione Formato  
6. R_Molecules 2021.pdf

accesso aperto

Tipologia: Versione finale editoriale
Licenza: Creative commons
Dimensione 2.05 MB
Formato Adobe PDF
2.05 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1216839
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact