PXD071008 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Lipid metabolism drives osimertinib resistance in non-small cell lung cancer |
| Description | Non-small-cell lung cancer (NSCLC) accounts for more than 80 % of lung cancer cases. Epidermal growth factor receptor mutations (EGFRm) occur in 15 % and 40 % of NSCLC in Western and Asian populations, respectively. Current treatment for advanced NSCLC targets EGFRm with tyrosine kinase inhibitors (TKIs). Osimertinib is a third generation EGFR-TKI now used as a first-line treatment in advanced/metastatic NSCLC, however drug resistance frequently develops. Dysregulation of metabolism has been suggested to play a role in development of drug resistance. Here, we investigated the role of lipid metabolism in the development of osimertinib resistance (OR) using pharmacologically-induced resistant cellular models. We used a multi-omics approach, combining lipidomics with proteomics analyses. We found alterations in processes relating to metabolism, including dysregulated sphingolipid metabolism, lipid peroxidation and ferroptosis. In particular, we identified that OR lines reduce free ceramides in favour of complex glycosphingolipids. Mechanistically, this metabolic shift avoids ceramide-mediated apoptosis via caspase 3 activation. Importantly, when we combined osimertinib with D-PDMP, an inhibitor of the key enzyme responsible for the conversion of ceramide to glucosylceramide, we increased sensitivity to osimertinib. Overall, we have identified the glycosphingolipid metabolic pathway as a potential therapeutic target to reinstate sensitivity to osimertinib in NSCLC. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-03-03 |
| AnnouncementXML | Submission_2026-03-03_04:42:37.949.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Alex Montoya |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | 2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
| Instrument | Orbitrap Exploris 240 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-11-20 13:18:58 | ID requested | |
| ⏵ 1 | 2026-03-03 04:42:38 | announced | |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Nonsmall-cell lung cancer |
| lipidomics |
| glycosphingolipid |
| ceramide |
| sphingolipid, drug resistance |
| multi-omics |
| glucosylceramidase |
Contact List
| Dr Zoe Hall |
|---|
| contact affiliation | Imperial College London |
| contact email | zoe.hall@imperial.ac.uk |
| lab head | |
| Alex Montoya |
|---|
| contact affiliation | London Institute of Medical Sciences |
| contact email | proteomics@lms.mrc.ac.uk |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD071008
- Label: PRIDE project
- Name: Lipid metabolism drives osimertinib resistance in non-small cell lung cancer
