PXD049477-1

PXD049477 is an original dataset announced via ProteomeXchange.

Title	Fasting boosts breast cancer therapy via glucocorticoid activation.
Description	The vast majority of all breast cancers are driven by oestrogen receptor alpha (ERα) activation, and endocrine therapy represents the mainstay treatment for these patients. However, resistance is common and tumours progress despite years of systemic endocrine suppression. Periodic fasting enhances the efficacy of standard endocrine drugs and delay acquired resistance to them, although the underlying mechanisms remain unclear. Here, we show that fasting, in combination with endocrine therapy, induces extensive epigenetic reprogramming in hormone receptor-positive (HR+) breast cancer xenografts, with large-scale activation of glucocorticoid receptor (GR) and progesterone receptor (PR) signalling, and impairment of activator protein-1 (AP-1) family activity. GR-driven gene programs were selectively activated after fasting, and GR knockout perturbed the beneficial effects of fasting in combination with tamoxifen, in vivo. Exogenous administration of GR-ligands fully recapitulated the observed fasting-enhanced anti-oestrogen action, resulting in tumour regression. Finally, elevated progesterone and cortisol levels were detected in the blood of breast cancer patients after fasting, thus providing clinical validation of our animal findings. Our results indicate GR activation to play a pivotal role in fasting’s ability to enhance endocrine drug activity against hormone-receptor positive breast cancer and suggest that corticosteroid administration should be evaluated as an adjuvant to endocrine therapy in this condition.
HostingRepository	PRIDE
AnnounceDate	2025-10-14
AnnouncementXML	Submission_2025-10-14_03:38:45.821.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liesbeth Hoekman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-19 02:54:40	ID requested
⏵ 1	2025-10-14 03:38:46	announced

Dataset with its publication pending

submitter keyword: glucocorticoid receptor, endocrine therapy, LC-MSMS, fasting, Human,Breast cancer

Onno Bleijerveld
contact affiliation	Mass Spectrometry/Proteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands.
contact email	o.bleijerveld@nki.nl
lab head
Liesbeth Hoekman
contact affiliation	The Netherlands Cancer Institute, Amsterdam, The Netherlands.
contact email	l.hoekman@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049477
     1. Label: PRIDE project
     2. Name: Fasting boosts breast cancer therapy via glucocorticoid activation.