In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 327-327
Abstract:
Major recent advances have recently been made in the understanding of the molecular pathways regulating the cell cycle machinery and their deregulations in cancer. These results open new avenues for the development of innovative antitumor pharmacological strategies targeting the cell cycle and its checkpoints. MultiCellular Tumor Spheroid (MCTS) are now considered as invaluable models to study cancer cell biology and for the preclinical development of new antiproliferative drugs. To fully exploit the features of MCTS, it is essential to preserve the 3D regionalization level of analysis when investigating the effect of a drug. We will report here a breakthrough in the use of MCTS with new technological developments that can be used to explore the regionalization and the live dynamics of the effects of anticancer drugs in 3D. Spheroids expressing fluorescent cell cycle reporters (i.e. Fucci) and biosensors were engineered and used to monitor cell cycle arrest and DNA damage Response (DDR) pathway activation induced by chemotherapeutic agents. The kinetics and regionalized aspects of the response were investigated on genetically modified spheroids using innovative 3D imaging strategy (based on 3D light sheet microscopy). We will present our latest results on the characterization of the effects of several anticancer drugs including DNA damaging agents alone or in association with checkpoint abrogating compounds. This study opens new perspectives for original 3D assays dedicated to the identification of new original targets and compounds and for the investigation of the dynamics of the 3D response to novel antiproliferative agents. Citation Format: Valérie LOBJOIS, Odile MONDESERT, Céline FRONGIA, Annaick DESMAISON, Aurélie GOMES, Martine CAZALES, Bernard Ducommun. 3D dynamics of the response to cell cycle checkpoint targeting drugs in multicellular tumour spheroids. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 327. doi:10.1158/1538-7445.AM2015-327
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-327
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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