Dataset Information

An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies

ABSTRACT: Oncogene addiction provides important therapeutic opportunities for precision oncology treatment strategies. To date the cellular circuitries associated with driving oncoproteins, which eventually establish the phenotypic manifestation of oncogene addiction remain largely unexplored. We employed a targeted mass spectrometry approach to systematically explore alterations in 116 phosphosites related to oncogene signaling and its intersection with the DDR following inhibition of the addicting oncogene alone or in combination with irradiation in MET-, EGFR-, ALK- or BRAF (V600)-positive cancer models and ex vivo non-small cell lung cancer patient organotypic cultures. We identified an ‘oncogene addiction phosphorylation signature’ (OAPS) consisting of 8 protein phosphorylations (ACLY S455, IF4B S422, IF4G1 S1231, LIMA1 S490, MYCN S62, NCBP1 S22, P3C2A S259 and TERF2 S365) that are significantly suppressed upon targeted oncogene inhibition solely in addicted cell line models and patient tissues. We show that the OAPS is present in patient tissues and the OAPS-derived score strongly correlates with the ex vivo responses to targeted treatments.

INSTRUMENT(S): Q TRAP

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell, Cell Culture

DISEASE(S): Lung Cancer

SUBMITTER: Michaela Medova

LAB HEAD: Yitzhak Zimmer

PROVIDER: PXD037406 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	DPs_SRM_heavy_light_iRT_daughter_plate_170302_phospho_final_transitions_final_peptides_tissues.sky	Other
	DPs_SRM_heavy_light_iRT_daughter_plate_170302_phospho_final_transitions_final_peptides_tissues.sky.view	Other
	DPs_SRM_heavy_light_iRT_daughter_plate_170302_phospho_final_transitions_final_peptides_tissues.skyd	Other
	EGFR.csv	Csv
	MET.csv	Csv

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An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.

Orlando Eleonora E Medo Matúš M Bensimon Ariel A Quintin Aurélie A Riedo Rahel R Roth Selina M SM Riether Carsten C Marti Thomas M TM Aebersold Daniel M DM Medová Michaela M Aebersold Ruedi R Zimmer Yitzhak Y

Cellular and molecular life sciences : CMLS 20221210 1

<h4>Purpose</h4>Oncogene addiction provides important therapeutic opportunities for precision oncology treatment strategies. To date the cellular circuitries associated with driving oncoproteins, which eventually establish the phenotypic manifestation of oncogene addiction, remain largely unexplored. Data suggest the DNA damage response (DDR) as a central signaling network that intersects with pathways associated with deregulated addicting oncoproteins with kinase activity in cancer cells.<h4>Ex ...[more]

PMID: 36494469

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