PXD023674-1

PXD023674 is an original dataset announced via ProteomeXchange.

Title	Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes: a Proof-of-Concept synthetic lethal study
Description	An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which binds multiple binding partners to suppress tumourigenesis via a number of different mechanisms. Approximately 45% of non-small cell lung cancers (NSCLC) are deficient in LIMD11, yet this subtype of NSCLC has been overlooked in preclinical and clinical investigations. Defining therapeutic targets in these LIMD1 loss-of-function patients is difficult due to a lack of ‘druggable’ targets, thus alternative approaches are required. To this end, we performed the first drug repurposing screen to identify synthetic lethal compounds with LIMD1 loss in lung cancer cells. PF-477736 was shown to selectively target LIMD1 deficient cells in vitro through inhibition of multiple kinases, inducing cell death via apoptosis. Furthermore, PF-477736 is effective in treating LIMD1-/- tumors in subcutaneous xenograft models, with no significant effect in LIMD1+/+ cells. We have identified a novel drug tool with significant preclinical characterization that serves as an excellent candidate to explore and define LIMD1-deficient cancers as a new therapeutic subgroup of critical unmet need.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_13:37:07.740.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023674
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pedro Casado-Izquierdo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-19 22:02:02	ID requested
⏵ 1	2022-02-16 13:37:08	announced

Davidson K, Grevitt P, Contreras-Gerenas MF, Bridge KS, Hermida M, Shah KM, Mardakheh FK, Stubbs M, Burke R, Casado P, Cutillas PR, Martin SA, Sharp TV, Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes. Cell Death Dis, 12(11):1075(2021) [pubmed]

submitter keyword: Synthetic Lethality, LIMD1, Tumour suppressor, Lung Cancer, NSCLC, targeted therapy

Pedro R. Cutillas
contact affiliation	Centre for Genomics and Computational Biology. Barts Cancer Institute / Queen Mary University of London
contact email	p.cutillas@qmul.ac.uk
lab head
Pedro Casado-Izquierdo
contact affiliation	Cell Signalling
contact email	p.m.casado-izquierdo@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023674
     1. Label: PRIDE project
     2. Name: Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes: a Proof-of-Concept synthetic lethal study