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PXD026805 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy
DescriptionStochastic transition of cancer cells between drug-sensitive and drug-tolerant persister phenotypes has been proposed to play a key role in non-genetic resistance to therapy. Yet, we show here that cancer cells actually possess a highly stable inherited chance to persist (CTP) during therapy. This CTP is non-stochastic, determined pre-treatment, and has a unimodal distribution ranging from 0 to almost 100%. Importantly, CTP is drug-specific. We found that differential serine/threonine phosphorylation of the insulin receptor substrate 1 (IRS1) protein determines the CTP of lung and of head and neck cancer cells under EGFR inhibition, both in vitro and in vivo. Indeed, the first-in-class IRS1 inhibitor NT219 was highly synergistic with anti-EGFR therapy across multiple in vitro and in vivo models. Elucidation of drug-specific mechanisms that determine the degree and stability of cellular CTP may establish a framework for the elimination of cancer persisters, using novel rationally designed drug combinations.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAmir Prior
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF; Orbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-18 06:52:16ID requested
12021-08-10 00:54:54announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Cancer, drug tolerant cells, cancer peristers, drug resistance, EGFR inhibition, IRS1, NSCLC
Contact List
Ravid Straussman
contact affiliationDepartment of Molecular Cell Biology, Weizmann institute of Science, Israel
contact emailRavidst@weizmann.ac.il
lab head
Amir Prior
contact affiliationWeizmann Institute of Science
contact emailamir.prior@weizmann.ac.il
dataset submitter
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Dataset FTP location
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