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| Status |
Public on Jan 23, 2018 |
| Title |
Targeting multiple effector pathways in pancreatic ductal adenocarcinoma with a G-quadruplex-binding small molecule |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Human pancreatic ductal adenocarcinoma (PDAC) involves the dysregulation of multiple signalling pathways. A novel approach to the treatment of PDAC is described, involving the targeting of cancer genes in PDAC pathways having over-representation of G-quadruplexes, using the quadruplex-binding compound CM03. This has been designed by computer modelling, is a potent inhibitor of cell growth in PDAC cell lines and has anti-cancer activity in PDAC models, with a superior profile compared to gemcitabine, a commonly used therapy. Whole-transcriptome RNA-seq methodology has been used to analyse for the first time the effects of a quadruplex-binding small molecule on gene expression. This has revealed the down-regulation of a large number of genes, rich in putative quadruplex elements and involved in essential pathways of PDAC survival, metastasis and drug resistance. The changes produced by CM03 represent a global response to the complexity of human PDAC, and may be applicable to other currently hard-to-treat cancers.
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| Overall design |
12 libraries for MIA PACA-2 cell line (6 and 24 hrs treatment with CM03 drug plus untreated control); 12 libraries for PANC-1 cell line (6 and 24 hrs treatment with CM03 drug plus untreated control); 28 libraries for MIA PACA-2 cell line (6 and 24 hrs treatment at 3 different concentrations with gemcitabine drug plus untreated control); 52 libraries for PANC-1 cell line (6 and 24 hrs treatment at 5 different concentrations with gemcitabine drug plus untreated control). Each condition has 3 or 4 biological replicates. See details below for concentration, treatment and replicates.
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| Contributor(s) |
Marchetti C, Zyner KG, Ohnmacht SA, Robson M, Haider SM, Morton JP, Marsico G, Vo T, Laughlin-Toth S, Ahmed AA, Di Vita G, Pazitna I, Gunaratnam M, Besser RJ, Gomes Andrade AC, Diocou S, Pike J, Tannahill D, Pedley RB, Evans TR, Wilson WD, Balasubramanian S, Neidle S |
| Citation(s) |
29356532, 32699225 |
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| Submission date |
Oct 17, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Giovanni Marsico |
| E-mail(s) |
persego@gmail.com
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| Organization name |
CRUK Cambridge Institute
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| Street address |
Robinson Way
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0RE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (104)
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| Relations |
| BioProject |
PRJNA414612 |
| SRA |
SRP120158 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE105083_RAW.tar |
9.4 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE105083_all.sum.htseq.txt.gz |
622.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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