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| Status |
Public on Sep 01, 2019 |
| Title |
Detoxifying doxorubicin |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The anthracycline doxorubicin is a highly effective anti-cancer drug associated with severe side effects, including secondary tumors and cardiotoxicity. Doxorubicin induces DNA damage through double-strand breaks (DSBs) and epigenetic or chromatin damage through histone eviction. We examined whether separation of these activities can help to detoxify doxorubicin, while maintaining its chemotherapeutic efficacy. We show that anthracycline variants harboring the histone eviction activity alone remain potent anti-cancer drugs, while greatly alleviating cardiotoxicity and secondary tumor formation. We thus demonstrate that treatment-limited side effects of doxorubicin can be synthesized away, yielding effective chemotherapeutics towards improved and prolonged treatment responses and higher patient quality of life.
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| Overall design |
Comparison of FAIRE-seq and yH2AX ChIP-seq signal for several anticancer drugs
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| Contributor(s) |
Qiao X, van de Zanden S, Wander D, Borras DM, van Tellingen O, Bakker J, Song J, Rutten A, van Gils N, Zuur C, Pang B, Smit L, Overkleeft H, Neefjes J |
| Citation missing |
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| Submission date |
Dec 18, 2017 |
| Last update date |
Sep 03, 2019 |
| Contact name |
Daniel M. Borras |
| E-mail(s) |
daniborras@gmail.com
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| Organization name |
LUMC
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| Department |
CI
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| Street address |
Einthovenweg 20
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| City |
Leiden |
| ZIP/Postal code |
2333 ZC |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA422761 |
| SRA |
SRP126929 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108179_RAW.tar |
13.2 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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