PXD059116

PXD059116 is an original dataset announced via ProteomeXchange.

Title	A targetable co-dependence of PI3Kα/δ and SUMO signaling in aggressive pancreatic cancer
Description	The phosphatidylinositol-3-kinase (PI3K) signaling pathway plays a critical role in the biology and aggressive course of pancreatic ductal adenocarcinoma (PDAC), yet pharmacological PI3K targeting has not resulted in meaningful clinical success. Through genetic and pharmacological screenings, we identified a targetable co-dependence between PI3K and the small ubiquitin-like modifier (SUMO) pathway in PDAC. Simultaneous inhibition of PIK3α and PIK3δ, combined with SUMO-activating E1 targeting, triggered synthetic lethality and an immunogenic cell death phenotype in preclinical models. In syngeneic orthotopic immune-competent PDAC models, this combination therapy reduced tumor growth and promoted T cell infiltration, signaling a strong antitumor response. The PI3Kα/δ and SUMO targeting approach thus shows potential for clinical translation and could form the basis for more effective therapies in PDAC, a cancer with significant unmet medical needs. This study introduces a combination therapy targeting the PI3K pathway and the SUMOylation pathway in pancreatic cancer. Combined PI3K and SUMOylation inhibition reveals preclinical efficacy including immune-modulatory effects in multiple pancreatic cancer models. The proposed combination therapy has the potential to provide transformative clinical benefits for pancreatic cancer patients.
HostingRepository	PRIDE
AnnounceDate	2026-02-22
AnnouncementXML	Submission_2026-02-22_14:06:03.794.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-21 09:01:45	ID requested
⏵ 1	2026-02-22 14:06:04	announced

K, ö, se H, Schneeweis C, Putze P, Contreras CT, Ferreiro L, Witte L, Deidda I, Herzberg F, Ebert S, Jakubik J, Moldaner L, Todorovic J, Tr, ä, ger I, Zang C, Demel UM, Hessmann E, Kirchner M, Rhein S, Hoffmann J, Tatarova Z, Ghadimi M, Saur D, Kappert K, Mertins P, Schneider G, Keller U, Wirth M, and Small Ubiquitin-Like Modifier Signaling in Pancreatic Cancer. Gastroenterology, 170(2):315-329(2026) [pubmed]

10.1053/j.gastro.2025.08.018;

submitter keyword: phsphorylation, Immunogenic cell death, SUMOylation, TMT,Pancreatic cancer, human, Combination therapy, PI3K

Philipp Mertins
contact affiliation	Core Unit Proteomics, Berlin Institute of Health at Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.
contact email	philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD059116

PRIDE project URI

• PRIDE
  1. PXD059116
     1. Label: PRIDE project
     2. Name: A targetable co-dependence of PI3Kα/δ and SUMO signaling in aggressive pancreatic cancer