Alignment between glioblastoma internal clock and environmental cues ameliorates survival in Drosophila

Abstract

Virtually every single living organism on Earth shows a circadian (i.e. “approximately a day”) internal rhythm that is coordinated with planet rotation (i.e. 24 hours). External cues synchronize the central clock of the organism. Consequences of biological rhythm disruptions have been extensively studied on cancer. Still, mechanisms underlying these alterations, and how they favor tumor development remain largely unknown. Here, we show that glioblastoma-induced neurodegeneration also causes circadian alterations in Drosophila. Preventing neurodegeneration in all neurons by genetic means reestablishes normal biological rhythms. Interestingly, in early stages of tumor development, the central pacemaker lengthens its period, whereas in later stages this is severely disrupted. The re-adjustment of the external light:dark period to longer glioblastoma-induced internal rhythms delays glioblastoma progression and ameliorates associated deleterious effects, even after the tumor onset.

Chronotherapy in Glioblastoma: state of the art and future perspectives

“…A study on Drosophila has shown that re-adjustment of the light/dark cycles delayed GBM progression. 114 In rats with glioma, constant light conditions resulted in increased tumour volume, compared to the light/dark conditions. 98 Moreover, it is also known that eating can act as a zeitgeber and lead to circadian entrainment through an increase in the levels of plasma glucose and insulin.…”

Socialization causes long-lasting behavioral changes

“…Adult brain preparations were stained following the same protocol as in 50 . Dissections were always performed at ZT4-5 to avoid possible circadian-induced changes.…”

An adult Drosophila glioma model to highlight metabolic dysfunctions and evaluate the role of the serotonin 5‐HT7 receptor as a potential therapeutic target

“…These two models have been widely used to identify new genes and signaling pathways involved in glioma progression. [41][42][43][44][45] Among the genes possibly involved in the progression of glioma, our recent data demonstrated the role of the serotonin 5-HT 7 receptor (5-HT 7 R) in a larval Drosophila model of glioma. 46 The human 5-HT 7 R expression in this animal model reduced larval lethality and partially restored dysregulated biomarkers.…”

“…The second model, established by Chi et al 40 , allowed to induce glioma development specifically at the adult stage. These two models have been widely used to identify new genes and signaling pathways involved in glioma progression 41–45 …”