From the Making of a Neural Lineage to the Making of a Tumor: Lessons from the "Simple" Drosophila Brain

Central nervous system (CNS) tumors are complex and highly heterogeneous, often associated with a poor prognosis. This inter-tumor heterogeneity arises not only from distinct genetic lesions but also from variations in the cell of origin and patient age. As a result, different CNS tumors necessitate highly specific treatment approaches. A comprehensive understanding of tumor biology is essential for the development of more effective and tailored therapeutic interventions. To achieve this, simple tumor models are invaluable for uncovering fundamental principles. The fruit fly Drosophila melanogaster serves as a powerful model organism for studying CNS development and its associated disorders. Extensive research has provided unprecedented insights into the principles of lineage progression, including asymmetric cell division, temporal patterning, and neuronal differentiation. More recently, Drosophila models of CNS tumors have been instrumental in uncovering key aspects of tumorigenesis. These include (i) how disruptions in lineage progression initiate tumorigenesis, (ii) how the cell of origin determines susceptibility to tumorigenesis and the cellular composition of tumors, (iii) how subversion of developmental programs governs tumor hierarchy and growth, and (iv) how metabolic switches drive uncontrolled proliferation. This chapter highlights recent advancements in the field and discusses future avenues of investigation where Drosophila will continue to contribute significantly to cancer research.