Strategies for Functional Interrogation of Big Cancer Data Using Drosophila Cancer Models

Abstract

Rapid development of high throughput genome analysis technologies accompanied by significant reduction in costs has led to the accumulation of an incredible amount of data during the last decade. The emergence of big data has had a particularly significant impact in biomedical research by providing unprecedented, systems-level access to many disease states including cancer, and has created promising opportunities as well as new challenges. Arguably, the most significant challenge cancer research currently faces is finding effective ways to use big data to improve our understanding of molecular mechanisms underlying tumorigenesis and developing effective new therapies. Functional exploration of these datasets and testing predictions from computational approaches using experimental models to interrogate their biological relevance is a key step towards achieving this goal. Given the daunting scale and complexity of the big data available, experimental systems like Drosophila that allow large-scale functional studies and complex genetic manipulations in a rapid, cost-effective manner will be of particular importance for this purpose. Findings from these large-scale exploratory functional studies can then be used to formulate more specific hypotheses to be explored in mammalian models. Here, I will discuss several strategies for functional exploration of big cancer data using Drosophila cancer models.

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

“…While this has yielded some clear gains, it is often tough to interpret this big cancer data and to translate it to improved patient care [116]. The way forward will be paved by functional studies in experimental models to reveal the biological significance of the newly identified variants [117]. Here, we sought to determine if tumors with different known initiating mutations share common cell biology in the form of signal pathway activity.…”

In silicological modelling to uncover cooperative interactions in cancer

“…It displays high levels of conservation in cancer relevant genes and signalling pathways. It supports easy and fast generations of lines carrying multiples mutated transgenes recapitulating mutational patterns observed in cancer samples as well as genetic modifier screens [10,20]. In addition, genetic tools developed in Drosophila allow to assess how genetically engineered cancer cells interact with their wild type neighbours or cooperate for their survival and expansion [10].…”

Basic and Translational Models of Cooperative Oncogenesis

“…Through decades of research, we have gained much knowledge on key molecular events and processes involved in the formation of cancer, and much of this knowledge has stemmed from investigations using model organisms, such as the mouse and the vinegar fly, Drosophila melanogaster, in addition to in vitro cell line studies. In this Special Issue, we present a collection of original research papers on various aspects of cancer research utilising human cell lines [7,8], or in vivo using Drosophila as a model system [9,10], as well as reviews highlighting the Drosophila model organism in cancer research [11][12][13][14][15]. Drosophila is a particularly useful model organism for the study of cancer mechanisms, because it has a rapid life cycle and is genetically manipulatable and since cancer genes and signalling pathways are highly conserved between humans and Drosophila, and interactions between tumour cells and surrounding normal cells can be readily examined in Drosophila tissues [6,[16][17][18][19][20].…”

“…The reviews in this Special Issue highlight the power of using Drosophila as an in vivo model system to study various aspects of cancer research, from its application in the study of the function of specific genes/pathways in cancer [11,15], to understanding particular cellular processes in cancer [13,14], and for functional analyses of cancer Omics data [12]. Sechi et al [15] review the mechanisms of the Golgi phosphoprotein 3 (GOLPH3) oncogene in cancer, covering research on human cancer samples, in vitro cell line analyses and Drosophila in vivo analyses.…”

“…Newman and Gregory [13] review the connection between chromosomal aberrations (aneuploidy) and metabolic changes, highlighting the role of oxidative stress and particularly reactive oxygen species (ROS) in this process. Finally, Bangi [12] reviews how Drosophila can be utilised to functionally analyse the vast amount of human cancer Omics data that is currently being generated, in order to validate key genes/pathways that contribute to cancer, to build new models to interrogate cancer mechanisms, and to screen for novel cancer therapeutics. Drosophila has already proven its worth in identifying novel drugs that target particular types of human cancers, such as multiple endocrine neoplasia type 2 (MEN2), colorectal and non-small cell lung cancers [36][37][38][39][40][41][42], and undoubtably, the development of more sophisticated Drosophila models that incorporate additional genetic lesions will enable better modelling of human cancers and new anti-cancer drug discovery.…”