![conference banner](/images/conference-banner.jpeg)
Abstract
Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.
Keywords: 3D culture, in vitro models, sarcoma, multicellular tumour spheroids (MCTS), cancer, high throughput screening (HTS).
[http://dx.doi.org/10.1038/nrc3087] [PMID: 21753790]
[http://dx.doi.org/10.1002/cncr.28657] [PMID: 24648013]
[http://dx.doi.org/10.1200/JCO.2009.26.1917] [PMID: 20194847]
(b)Bovée, J.V.; Hogendoorn, P.C. Molecular pathology of sarcomas: concepts and clinical implications. Virchows Arch., 2010, 456(2), 193-199.
[http://dx.doi.org/10.1007/s00428-009-0828-5] [PMID: 19787372]
[http://dx.doi.org/10.1111/his.12267] [PMID: 24164390]
[http://dx.doi.org/10.1097/PAS.0000000000000286] [PMID: 25007147]
(b)Graham, C.; Chilton-MacNeill, S.; Zielenska, M.; Somers, G.R. The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas. Hum. Pathol, 2012, 43(2), 180-189.
[http://dx.doi.org/10.1016/j.humpath.2011.04.023] [PMID: 21813156]
[http://dx.doi.org/10.1097/PAS.0000000000000223] [PMID: 24805859]
[http://dx.doi.org/10.1038/362857a0] [PMID: 8479525]
[http://dx.doi.org/10.1038/363640a0] [PMID: 8510758]
[http://dx.doi.org/10.2147/OTT.S127955] [PMID: 28260930]
[http://dx.doi.org/10.1016/S1470-2045(16)30050-X] [PMID: 27210906]
[http://dx.doi.org/10.1093/annonc/mdu254] [PMID: 25210080]
[http://dx.doi.org/10.1016/S1470-2045(14)70063-4] [PMID: 24618336]
[http://dx.doi.org/10.1186/s12885-015-1697-8] [PMID: 26472661]
(b)Sanfilippo, R.; Dileo, P.; Blay, J.Y.; Constantinidou, A.; Le Cesne, A.; Benson, C.; Vizzini, L.; Contu, M.; Baldi, G.G.; Dei Tos, A.P.; Casali, P.G. Trabectedin in advanced synovial sarcomas: a multicenter retrospective study from four European institutions and the Italian Rare Cancer Network. Anticancer Drugs, 2015, 26(6), 678-681.
[PMID: 25763543]
[http://dx.doi.org/10.1016/S0140-6736(15)01283-0] [PMID: 26874885]
[http://dx.doi.org/10.1200/JCO.2003.04.190] [PMID: 14645423]
(b)Poveda, A.; del Muro, X.G.; López-Guerrero, J.A.; Martínez, V.; Romero, I.; Valverde, C.; Cubedo, R.; Martín-Broto, J. GEIS 2013 guidelines for gastrointestinal sarcomas (GIST). Cancer Chemother. Pharmacol, 2014, 74(5), 883-898.
[http://dx.doi.org/10.1007/s00280-014-2547-0] [PMID: 25193432]
[http://dx.doi.org/10.1097/CCO.0b013e328353d78d] [PMID: 22510939]
(b)McArthur, G.A.; Demetri, G.D.; van Oosterom, A.; Heinrich, M.C.; Debiec-Rychter, M.; Corless, C.L.; Nikolova, Z.; Dimitrijevic, S.; Fletcher, J.A. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J. Clin. Oncol., 2005, 23(4), 866-873.
[http://dx.doi.org/10.1200/JCO.2005.07.088] [PMID: 15681532]
[http://dx.doi.org/10.1016/S0140-6736(12)60651-5] [PMID: 22595799]
[http://dx.doi.org/10.1016/S0140-6736(16)30788-7] [PMID: 27291995]
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0831] [PMID: 26330427]
(b)Silveira, S.M.; Villacis, R.A.; Marchi, F.A. Barros Filho, Mde.C.; Drigo, S.A.; Neto, C.S.; Lopes, A.; da Cunha, I.W.; Rogatto, S.R. Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas. PLoS One, 2013, 8(6), e67643.
[http://dx.doi.org/10.1371/journal.pone.0067643] [PMID: 23825657]
[http://dx.doi.org/10.1159/000104451] [PMID: 17709966]
[http://dx.doi.org/10.1016/j.molonc.2008.07.004] [PMID: 19383342]
[http://dx.doi.org/10.1038/nature11003] [PMID: 22460905]
[http://dx.doi.org/10.1038/nature08768] [PMID: 20164919]
[http://dx.doi.org/10.1016/j.cell.2007.08.006] [PMID: 17719539]
[http://dx.doi.org/10.1242/jcs.079509] [PMID: 22797912]
(b)Minchinton, A.I.; Tannock, I.F. Drug penetration in solid tumours. Nat. Rev. Cancer, 2006, 6(8), 583-592.
[http://dx.doi.org/10.1038/nrc1893] [PMID: 16862189]
[PMID: 9721858]
[http://dx.doi.org/10.1016/j.jbiotec.2010.01.012] [PMID: 20097238]
[PMID: 128440]
(b)Sutherland, R.M.; Sordat, B.; Bamat, J.; Gabbert, H.; Bourrat, B.; Mueller-Klieser, W. Oxygenation and differentiation in multicellular spheroids of human colon carcinoma. Cancer Res., 1986, 46(10), 5320-5329.
[PMID: 3756881]
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0074] [PMID: 26351324]
[http://dx.doi.org/10.3791/2720] [PMID: 21587162]
[http://dx.doi.org/10.1186/1741-7007-10-29] [PMID: 22439642]
[http://dx.doi.org/10.1177/2211068216652846] [PMID: 27272155]
[http://dx.doi.org/10.1089/adt.2016.737] [PMID: 27552143]
[http://dx.doi.org/10.1371/journal.pone.0169407] [PMID: 28056055]
[PMID: 14522905]
[PMID: 19360350]
(b)Gibbs, C.P.; Kukekov, V.G.; Reith, J.D.; Tchigrinova, O.; Suslov, O.N.; Scott, E.W.; Ghivizzani, S.C.; Ignatova, T.N.; Steindler, D.A. Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia, 2005, 7(11), 967-976.
[http://dx.doi.org/10.1593/neo.05394] [PMID: 16331882]
[http://dx.doi.org/10.1002/ijc.25163] [PMID: 20104521]
[http://dx.doi.org/10.3892/ijo.2013.1826] [PMID: 23416969]
[http://dx.doi.org/10.3892/ijo.2013.1927] [PMID: 23636271]
[http://dx.doi.org/10.3171/2011.12.JNS11430] [PMID: 22283189]
[http://dx.doi.org/10.1186/s13046-015-0175-0] [PMID: 26055407]
[http://dx.doi.org/10.1089/adt.2014.573] [PMID: 24831787]
[http://dx.doi.org/10.1073/pnas.1221403110] [PMID: 23576741]
[http://dx.doi.org/10.1038/labinvest.2013.101] [PMID: 23958880]
[http://dx.doi.org/10.18632/oncotarget.4140] [PMID: 26203049]
[http://dx.doi.org/10.1371/journal.pcbi.1007053] [PMID: 31185009]
[http://dx.doi.org/10.18632/oncotarget.5874] [PMID: 26528856]
[http://dx.doi.org/10.1016/j.biotechadv.2014.07.009] [PMID: 25116894]
[http://dx.doi.org/10.1016/j.addr.2014.07.012] [PMID: 25109853]
[http://dx.doi.org/10.1089/ten.tea.2013.0256] [PMID: 23799306]
[http://dx.doi.org/10.1016/j.addr.2014.05.003] [PMID: 24819215]
[PMID: 5101993]
[http://dx.doi.org/10.1126/science.1247125] [PMID: 25035496]
[http://dx.doi.org/10.1038/s41416-018-0359-4] [PMID: 30745580]
![Wayfinder Image](/images/wayfinder.jpg)