Chemical genetics and drug screening in Drosophila cancer models

Mara Gladstone; Tin Tin Su

doi:10.1016/j.jgg.2011.09.003

Volume 38 Issue 10

Oct. 2011

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Chemical genetics and drug screening in Drosophila cancer models

doi: 10.1016/j.jgg.2011.09.003

Mara Gladstone^{a, b},
Tin Tin Su^a

a
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA
b
SuviCa, Inc., Box 3131, Boulder, CO 80307-3131, USA

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Corresponding author: E-mail address: Tin.su@colorado.edu (Tin Tin Su)
Received Date: 2011-08-10
Accepted Date: 2011-09-10
Rev Recd Date: 2011-09-10

Available Online: 2011-09-17

Publish Date: 2011-10-20

Abstract

Abstract

Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety. It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later. In this regard, it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays. Drosophila melanogaster has emerged as a potential whole animal model for drug screening. Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer. A recent review provides a comprehensive summary of drug screening in Drosophila, but with an emphasis on neurodegenerative disorders. Here, we review Drosophila screens in the literature aimed at cancer therapeutics.
- Cancer,
- Drug screening

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References(62)

References

[1]	Arbouzova, N.I., Zeidler, M.P. Development, 133 (2006),pp. 2605-2616
[2]	Barker, N., Clevers, H. Mining the Wnt pathway for cancer therapeutics Nat. Rev. Drug Discov., 5 (2006),pp. 997-1014
[3]	Bergantinos, C., Vilana, X., Corominas, M. et al. Imaginal discs: renaissance of a model for regenerative biology Bioessays, 32 (2010),pp. 207-217
[4]	Bhandari, P., Shashidhara, L.S. Oncogene, 20 (2001),pp. 6871-6880
[5]	Brumby, A.M., Richardson, H.E. EMBO J., 22 (2003),pp. 5769-5779
[6]	Brumby, A.M., Richardson, H.E. Nat. Rev. Cancer, 5 (2005),pp. 626-639
[7]	Carlomagno, F., Vitagliano, D., Guida, T. et al. ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases Cancer Res., 62 (2002),pp. 7284-7290
[8]	Caussinus, E., Gonzalez, C. Nat. Genet., 37 (2005),pp. 1125-1129
[9]	Chia, I.V., Costantini, F. Mol. Cell. Biol., 25 (2005),pp. 4371-4376
[10]	Cohen, S.
[11]	Das, T., Cagan, R. Thyroid, 20 (2010),pp. 689-695
[12]	DeGregori, J., Johnson, D.G. Distinct and overlapping roles for E2F family members in transcription, proliferation and apoptosis Curr. Mol. Med., 6 (2006),pp. 739-748
[13]	Dow, L.E., Elsum, I.A., King, C.L. et al. Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling Oncogene, 27 (2008),pp. 5988-6001
[14]	Edgar, B.A., Weir, M.P., Schubiger, G. et al. Cell, 47 (1986),pp. 747-754
[15]	Edwards, A., Gladstone, M., Yoon, P. et al. Dis. Model Mech., 4 (2011),pp. 496-503
[16]	Fan, Y., Bergmann, A. Apoptosis-induced compensatory proliferation. The cell is dead. Long live the cell! Trends Cell Biol., 18 (2008),pp. 467-473
[17]	Fan, Y., Bergmann, A. Dev Cell., 14 (2008),pp. 399-410
[18]	Feany, M.B., Bender, W.W. Nature, 404 (2000),pp. 394-398
[19]	Frolov, M.V., Huen, D.S., Stevaux, O. et al. Functional antagonism between E2F family members Genes Dev., 15 (2001),pp. 2146-2160
[20]	Gladstone, M., Su, T.T.
[21]	Gonsalves, F.C., Klein, K., Carson, B.B. et al. An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway Proc. Natl. Acad. Sci. USA, 108 (2011),pp. 5954-5963
[22]	Gregorieff, A., Clevers, H. Wnt signaling in the intestinal epithelium: from endoderm to cancer Genes Dev., 19 (2005),pp. 877-890
[23]	Hariharan, I.K., Bilder, D. Annu. Rev. Genet., 40 (2006),pp. 335-361
[24]	He, T.C., Sparks, A.B., Rago, C. et al. Identification of c-MYC as a target of the APC pathway Science, 281 (1998),pp. 1509-1512
[25]	Hijazi, A., Haenlin, M., Waltzer, L. et al. PLoS ONE, 6 (2011),p. e17763
[26]	Hirsh, J.
[27]	Humbert, P.O., Grzeschik, N.A., Brumby, A.M. et al. Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module Oncogene, 27 (2008),pp. 6888-6907
[28]	Jackson, G.R., Salecker, I., Dong, X. et al. Neuron, 21 (1998),pp. 633-642
[29]	Jackson, G.R., Wiedau-Pazos, M., Sang, T.K. et al. Neuron, 34 (2002),pp. 509-519
[30]	Jaklevic, B., Uyetake, L., Lemstra, W. et al. Genetics, 174 (2006),pp. 1963-1972
[31]	Januschke, J., Gonzalez, C. Oncogene, 27 (2008),pp. 6994-7002
[32]	Jiang, H., Edgar, B.A. Development, 136 (2009),pp. 483-493
[33]	Juang, J.L., Carlson, S.D. Cell Tissue Res., 277 (1994),pp. 87-95
[34]	Karess, R. Rod-Zw10-Zwilch: a key player in the spindle checkpoint Trends Cell Biol., 15 (2005),pp. 386-392
[35]	Kim, B.H., Yin, C.H., Guo, Q. et al. A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells Mol. Cancer Ther., 7 (2008),pp. 2672-2680
[36]	Martin, F.A., Herrera, S.C., Morata, G. Development, 136 (2009),pp. 3747-3756
[37]	Martin, F.A., Perez-Garijo, A., Morata, G. Int. J. Dev. Biol., 53 (2009),pp. 1341-1347
[38]	Micchelli, C.A., Perrimon, N. Nature, 439 (2006),pp. 475-479
[39]	Orr, B., Afonso, O., Feijao, T. et al. Biochem. Soc. Trans., 38 (2010),pp. 1667-1675
[40]	Pagliarini, R.A., Xu, T. Science, 302 (2003),pp. 1227-1231
[41]	Pan, D., Dong, J., Zhang, Y. et al. Trends Cell Biol., 14 (2004),pp. 78-85
[42]	Pandey, U.B., Nichols, C.D. Pharmacol. Rev., 63 (2011),pp. 411-436
[43]	Peel, D.J., Johnson, S.A., Milner, M.J. The ultrastructure of imaginal disc cells in primary cultures and during cell aggregation in continuous cell lines Tissue Cell, 22 (1990),pp. 749-758
[44]	Polakis, P. The many ways of Wnt in cancer Curr. Opin. Genet. Dev., 17 (2007),pp. 45-51
[45]	Radimerski, T., Montagne, J., Hemmings-Mieszczak, M. et al. Genes Dev., 16 (2002),pp. 2627-2632
[46]	Read, R.D., Goodfellow, P.J., Mardis, E.R. et al. Genetics, 171 (2005),pp. 1057-1081
[47]	Repiso, A., Bergantinos, C., Corominas, M. et al. Dev. Growth Differ., 53 (2011),pp. 177-185
[48]	Romero-Calderon, R., Krantz, D.E. Biochem. J., 393 (2006),pp. 583-589
[49]	Rothenberg, S.M., Mohapatra, G., Rivera, M.N. et al. A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers Cancer Res., 70 (2010),pp. 2158-2164
[50]	Rutkowski, R., Hofmann, K., Gartner, A. Phylogeny and function of the invertebrate p53 superfamily Cold Spring Harb. Perspect. Biol., 2 (2010),p. a001131
[51]	Ryoo, H.D., Baehrecke, E.H. Curr. Opin. Cell Biol., 22 (2010),pp. 889-895
[52]	Ryoo, H.D., Gorenc, T., Steller, H. Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways Dev. Cell, 7 (2004),pp. 491-501
[53]	Shermoen, A.
[54]	Su, T.T. Cellular responses to DNA damage: one signal, multiple choices Annu. Rev. Genet., 40 (2006),pp. 187-208
[55]	Tsen, C., Iltis, M., Kaur, N. et al. J. Med. Chem., 51 (2008),pp. 324-330
[56]	Vidal, M., Cagan, R.L. Curr. Opin. Genet. Dev., 16 (2006),pp. 10-16
[57]	Vidal, M., Wells, S., Ryan, A. et al. Cancer Res., 65 (2005),pp. 3538-3541
[58]	Wu, M., Pastor-Pareja, J.C., Xu, T. Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion Nature, 463 (2010),pp. 545-548
[59]	Yamaguchi, M., Hirose, F., Inoue, Y.H. et al. Oncogene, 18 (1999),pp. 6767-6775
[60]	Yu, C.L., Meyer, D.J., Campbell, G.S. et al. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein Science, 269 (1995),pp. 81-83
[61]	Yu, H., Jove, R. The STATs of cancer—new molecular targets come of age Nat. Rev. Cancer, 4 (2004),pp. 97-105
[62]	Yu, H., Pardoll, D., Jove, R. STATs in cancer inflammation and immunity: a leading role for STAT3 Nat. Rev. Cancer, 9 (2009),pp. 798-809