Modeling colorectal cancer as a 3-dimensional disease in a dish: the case for drug screening using organoids, zebrafish, and fruit flies

Abstract

This review discusses recent shifts in the understanding of colorectal cancer as a stem cell based disease, based on findings that tie patient prognosis to the presence of cancer stem cells in colorectal tumors. Currently no drugs specifically target CSCs in colorectal tumors.However, recent advances in the culturing of colorectal stem cells using mammalian organoids, zebrafish, and Drosophila offer promising avenues for anti-CSC drug discovery.

Modelling Cooperative Tumorigenesis inDrosophila

“…Due to its sophisticated genetics, Drosophila will continue to play an important role in revealing the function of cancer-causing genes in vivo and elucidating their mechanisms of action in cooperative tumorigenesis. Moreover, Drosophila is now emerging as a highly suitable model organism for the discovery of anticancer compounds against various cancer types, which can be then developed for clinical use, with reduced need for animal models (reviewed in [ 3 , 10 , 13 , 14 , 282 , 283 ]). Thus, in the new age of pharmacogenetics, Drosophila will continue to play a fruitful role in elucidating new cooperative gene interactions in cancer and identifying anticancer compounds that then can be harnessed for anticancer therapy.…”

Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back

“…The utility of the model in combination therapy and drug uptake/bioavailability is also discussed. Brain cancer PDGF, EGFR, PI3K, Notch [106][107][108][109] Medullary thyroid carcinoma RET, Ras, EGFR, ERK [30,32,34,110] Tuberous sclerosis TSC-1, TSC-2 [111,112] Colorectal cancer Wnt, EGFR, Ras [40,113,114] Prostate cancer MRGBP, CNPY2, MEP1A [115] Ovarian cancer YAP/Hippo [116] Skin cancer Hh/Ptc [117] Drosophila in Cancer Drug Discovery…”

Systematic screen of chemotherapeutics in Drosophila stem cell tumors

“…Efforts are underway to more precisely culture and screen stem cells cocultured with their niche (19,20). However, an alternative approach that is more immediately available is to use the ready-made stem cell microenvironments found in living animals, which can be probed by performing whole-animal screens (21).…”