PXD065390 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A potent cytidine deaminase biodegrader sensitises cancer cells to deoxycytidine analogue-based chemotherapies |
| Description | Deoxycytidine analogues (dC) are chemotherapy agents used to treat a range of solid and blood cancers. However, their clinical efficacy is often limited by resistance mechanisms. Cytidine deaminase (CDA) plays a key role of this resistance by deaminating dC analogues into inactive metabolites. Although pharmacological inhibitors targeting the CDA catalytic site have been developed, they exhibit limited efficacy and off-target effects. To overcome these limitations, alternative strategies to target CDA are needed. Here, we develop a CDA biodegrader using a cell-based screening approach. This biodegrader consists of an intracellular anti-CDA VHH fused to the SPOP E3 ubiquitin ligase. We demonstrate that the CDA biodegrader is highly specific and effectively depletes CDA across various pancreatic, lung, and acute myeloid leukaemia (AML) cancer cell lines. Furthermore, it sensitises these cells to dC analogue treatment in vitro. CDA-targeted degradation combined with gemcitabine leads to regression of pancreatic and lung tumours in vivo. These findings highlight CDA degradation as a promising therapeutic strategy to enhance the efficacy of dC analogues in cancer treatment. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-08-24 |
| AnnouncementXML | Submission_2026-08-24_02:28:23.681.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Alexandre STELLA |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | iodoacetamide derivatized residue |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-06-24 04:28:24 | ID requested | |
| ⏵ 1 | 2026-08-24 02:28:24 | announced | |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: targeted protein degradation, cytarabine, cytidine deaminase, chemotherapy resistance, single domain antibody, lung cancer,biodegrader, pancreatic cancer, gemcitabine |
Contact List
| Odile Schiltz |
|---|
| contact affiliation | Institut de Pharmacologie et de Biologie Structurale Équipe "Protéomique et Spectrométrie de Masse de Biomolécules" ProteoToul Toulouse 205, route de Narbonne - BP 64182 - 31077 Toulouse Cedex - France |
| contact email | Odile.Schiltz@ipbs.fr |
| lab head | |
| Alexandre STELLA |
|---|
| contact affiliation | CNRS |
| contact email | alexandre.stella@ipbs.fr |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD065390
- Label: PRIDE project
- Name: A potent cytidine deaminase biodegrader sensitises cancer cells to deoxycytidine analogue-based chemotherapies
