Modeling Tumorigenesis in Drosophila: Current Advances and Future Perspectives

Abstract

Cancer is essentially considered to be a genetic disease caused by the accumulation of multiple genetic or epigenetic lesions in tumor-suppressor genes and oncogenes [1]. Although the notion that retinoblastoma could be an inherited disease was already formulated at the end of the 19th Century, a solid genetic basis was established with the discovery of both protooncogenes, whose gain-of function mutations or altered expression is associated with the cancerous state, and tumor suppressor genes (TSGs), whose inactivation releases the “brakes” inhibiting cell proliferation. Analysis of both proto-oncogenes and TSGs revealed also that cancer results from an alteration of the normal pathway of cell fate and differentiation. The hallmarks of cancer, as laid down by Hanahan and Weinberg to explain the complex biology of cancer, comprise of six major developmental changes taking successively place in human tumors. These cancer “characteristics” include sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis as well as cell invasion and metastasis. Underlying these hallmarks are genome instability, inflamma‐ tion, reprogramming of energy metabolism and evading immune destruction [2].