Updated project metadata. The present study is a pioneering investigation that has been carefully designed to study proteomic effects of specific cancer-related mutation using the lgl mutant of D. melanogaster that has not been well characterised thus far. Recent findings concerning the D. melanogaster cancer models suggest that this model is well suited for study of cancer mechanisms and therapeutic interventions, especially in the brain and intestines (Mirzoyan et al., 2019). In addition, the integration of circadian biology into cancer research offers new insights into the implications of optimal timing for cancer treatment that could potentially reduce undesirable side effects and enhance prognosis (Ballesta et al., 2017). As a result, label free quantitative mass spectrometry was employed to investigate tissue-specific protein expression in head and intestinal tissues of D. melanogaster lgl mutants which was collected at 6-hours intervals throughout the 24-hour period. Furthermore, the efficacy of melatonin as an anticancer agent at the proteome level was also investigated. Together, the resulting information could potentially identify malfunctioning signalling pathways and circadian rhythm-dependent protein markers during tumorigenesis, as well as the mechanism of actions of melatonin on these processes, post-treatment