Phase II study of alisertib, irinotecan, and temozolomide in children with relapsed and refractory neuroblastoma: A report from the New Approaches to Neuroblastoma Therapy (NANT) consortium.

The Myc Family and the Metastasis Suppressor NDRG1: Targeting Key Molecular Interactions with Innovative Therapeutics

“…Unfortunately, clinical trials have established that Aurora-A inhibitors have unexpected adverse events such as neutropenia (Seymour et al, 2014), fatigue/asthenia, nausea, diarrhea, anorexia, vomiting, alopecia, constipation, and pyrexia (Schöffski et al, 2015). The combination of Aurora-A inhibitors with other anticancer drugs also has promising anti-tumor activity and has successfully entered phase I clinical studies as a new approach to NB therapy (DuBois et al, 2016).…”

“…Considering promising future therapeutic directions, there have been a number of preclinical studies or clinical trials conducted based on targeting protein-protein interactions that have achieved promising results. For instance, a phase I clinical trial revealed that the combination of the Aurora-A inhibitor, alisertib, the topoisomerase I inhibitor, irinotecan, and the alkylating agent, temozolomide, showed a promising response rate compared to NB patients treated with alisertib alone (Bagatell et al, 2011;DuBois et al, 2016;Mossé et al, 2019).…”

Emerging and investigational therapies for neuroblastoma

“…In preclinical testing, the AURKA inhibitor alisertib (MLN8237) led to a complete response in three out of seven neuroblastoma xenografts [89]. A recent NANT Phase 1/2 study demonstrated that alisertib is well tolerated and an objective response was seen in 6 of 32 (18.8%) patients taking either the tablet or solution formulation [90]. Somewhat paradoxically, patients with MYCN -amplification had a trend towards lower response rates, necessitating improved biomarkers of activity in future trials of this agent.…”