Aiming at neuroblastoma and hitting other worthy targets

Abstract

Neuroblastoma is, at once, the most common and deadly extracranial solid tumor of childhood. Efforts aimed at targeting the neural characteristics of these tumors have taught us much about neural crest cell biology, apoptosis induction in the nervous system, and neurotrophin receptor signaling and intracellular processing. But neuroblastoma remains a formidable enemy to the oncologist and an enigmatic target to the neuroscientist.

Keywords: apoptosis; neural crest tumors; neurotrophin receptors.

Figure 1.

Amifostine (R-S-OPO3) is preferentially cleaved to a sulfhydryl (R-SH) in normal cells relative to tumor cells. In these normal cells, R-SH acts as an antioxidant, reducing reactive oxygen species and, in turn, becoming oxidized (to R-S-S-R) itself. R-S-S-R reacts with γ-glutamylcysteine synthetase, the rate-limiting enzyme for glutathione synthesis, and glutathione synthesis ceases.

Figure 2.

p75NTR is a trans-membrane protein. Cleavage of p75NTR by α- and γ-secretase (labelled “γ”) liberates its intracellular domain (p75ICD). p75ICD is thought to translocate to the nucleus and mitochondria, altering its transcriptome and redox state.