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| Status |
Public on May 16, 2022 |
| Title |
Decreased serine biosynthesis identifies a subgroup of platinum resistant ovarian cancers and novel actionable metabolic vulnerabilities |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, particularly epithelial ovarian cancer. After initial response, patients often experience several response-relapse events, until tumors start to resist the treatment. Resistant patients have low response rate to other chemotherapy regimens, with life expectancy of 12-15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, and no novel drugs have been approved for resistant disease. By investigating the functional link between metabolic adaptations and resistance, we discovered that resistant cells modify their serine metabolism and acquire a specific NAD+ generating phenotype, which allows them to sustain PARP activity under treatment. Our findings reveal a novel metabolic vulnerability of resistant tumors that might have an immediate clinical implication, showing that ex vivo patient derived resistant models can be re-sensitized to platinum by combining it with PARP inhibition.
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| Overall design |
RNA sequencing of A2780 and cisplatin-resistant A2780 cells.
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| Contributor(s) |
Van Nyen T, Planqu M, van Wagensveld L, Duarte JA, Zaal EA, Talebi A, Rossi M, Körner PR, Rizzotto L, Moens S, De Wispelaere W, Eelen G, Berardi E, Swinnen JV, Berkers CR, Carmeliet P, Lambrechts D, Davidson B, Agami R, Fendt SM, Annibali D, Amant F |
| Citation(s) |
35931688 |
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| Submission date |
Jun 05, 2021 |
| Last update date |
Aug 15, 2022 |
| Contact name |
Pierre-Rene Körner |
| Organization name |
Netherlands Cancer Institute (NKI)
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| Department |
Oncogenomics
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| Street address |
Plesmanlaan 121
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| City |
Amsterdam |
| ZIP/Postal code |
1066CX |
| Country |
Netherlands |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA735397 |
| SRA |
SRP322864 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE176218_RNAseq_readscounts.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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