Is Neuroblastoma A Case of Viral Mimicry Suppression?

Generalization and paradigms in Cancer Research are useful but easily lead to conundrums, confusion or paradoxes, as shown here by contraposing two generally accepted “keywords” such as “Targeted Gene Theray” (TGT) and “Viral Mimicry” (VM). The initial approach to oncogene abnormalities was epitomized by the 1989 Weinberg’s paper: “throwing monkey wrenches into the clock”: although we now throw smart small and efficacious molecules, the general approach has not changed. It was believed that curing the gene would cure the disease and nobody asked why such mutations appeared in the first place. We realize today that TGTs are short-lasting. Recently, several groups, working on adult cancers, emphasized the new concept of Viral Mimicry (VM), which sheds new light on the origin of oncogene mutations. Accordingly, oncogene mutations appear as strong suppressors of VM programs: inactivating mutated oncogenes permits the full-blown apoptotic VM program to take place. Initial VM activation is believed to be predominantly associated with dsRNA of Endogenous Elements (EE), but other types of daRNAs have been described. In Neuroblastoma -where VM has been practically ignored- we discovered and isolated a dsRNA virus (MFV) associated with VM death and activation of dsRNA helicases, which is counteracted by DNA amplification of the MYCN proto-oncogene. It is therefore suggested that further research on VM should be extended also to pediatric cancers and especially Neuroblastoma, since it provides a logic explanation for the Darwinian forces, which select for and determine the otherwise unexplainable MYCN amplifications phenomena.