1000P Screening cancer immunotherapeutic agents using high content imaging and analysis of immune-competent 3D InSight tumor models

2021 ◽  
Vol 32 ◽  
pp. S849
Author(s):  
F. Chiovaro ◽  
I. Agarkova ◽  
P. Vonschallen ◽  
S. Strebel ◽  
A. Wolf
2019 ◽  
Author(s):  
Daniel Sun ◽  
Soumya Poddar ◽  
Roy D. Pan ◽  
Juno Van Valkenburgh ◽  
Ethan Rosser ◽  
...  

The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone <b>HCT-13</b>, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC<sub>90</sub> values in the low-to-mid nanomolar range.<b> </b>We show that the cytotoxicity of <b>HCT-13</b> is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following <b>HCT-13 </b>treatment. Taken together, <b>HCT-13 </b>is potent against solid tumor models and warrants <i>in vivo</i> evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.


2004 ◽  
Vol 4 (4) ◽  
pp. 419-430 ◽  
Author(s):  
E. Graves ◽  
R. Weissleder ◽  
V. Ntziachristos

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