Drosophila cancer models

Abstract

Cancer is driven by complex genetic and cellular mechanisms. Recently, the Drosophila community has become increasingly interested in exploring cancer issues. The Drosophila field has made seminal contributions to many of the mechanisms that are fundamental to the cancer process; several of these mechanisms have already been validated in vertebrates. Less well known are the Drosophila field's early direct contributions to the cancer field: some of the earliest tumor suppressors were identified in flies. In this review, we identify major contributions that Drosophila studies have made toward dissecting the pathways and mechanisms underlying tumor progression. We also highlight areas, such as drug discovery, where we expect Drosophila studies to make a major scientific impact in the future.

Impaired Hippo signaling promotes Rho1–JNK-dependent growth

“…Similarly, JNK signaling plays a major role in modulating metastasis in both flies and mammals (38,39). Rho1 was also reported to cooperate with oncogenic Ras to induce large invasive tumors (40).…”

Evaluating Drosophila p53 as a Model System for Studying Cancer Mutations

“…This suggests that retaining the wildtype conformation of the L3 loop is essential for correct positioning of the DNA contact residue Arg-234 in Dmp53 (and potentially also for mediating DBD-DBD interactions upon binding to target DNA as a tetramer, as reported for Hp53 (39)). In recent years, Drosophila has attracted increased interest as a model organism for studying the evolution of tumor suppressor pathways and their deregulation in cancer (18,40). Despite the low sequence conservation between Dmp53 and Hp53, many structural and functional features, in particular the DNA binding specificity, are conserved.…”

Focused chemical genomics using zebrafish xenotransplantation as a pre-clinical therapeutic platform for T-cell acute lymphoblastic leukemia

“…15 Murine models offer the ability to screen and evaluate anti-cancer agents prior to pre-clinical assessment; however, the associated cost is substantial and the time it takes to complete these studies can be extensive and not compatible with patient-directed interventions in an actionable time frame. Primary human T-ALL cells are not sustainable in culture and while T-ALL cell lines have shown utility for drug screening, they are unable to inform individual patient treatment decisions.…”