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Data · dataset · 2026

Identification of MEN1 loss-off function as a potential biomarker for immune checkpoint therapy

Listed in ZivaHub and Deakin Research Online and DMU Figshare and UCL Research Data Repository — shown once because both records carry DOI 10.17034/32632527.v1

Immune-based therapies are an emerging field in the treatment of cancers, with immune checkpoint inhibitor therapies proving to be particularly effective, even in typically hard to treat cancers.

Description

Despite effective immune checkpoint therapies now being available, it is still difficult to predict response to treatment and therefore stratify patient care. Blockade of PD- 1/PD-L1 (Programmed death receptor (ligand) 1) has shown potent antitumor activity but therapies are limited by a lack of patient stratification.

It was hypothesised that loss of tumour suppressor genes (TSGs), not previously known to induce immunogenicity, could upregulate PD-L1 expression, and if this occurred alongside an increase in tumour immunogenicity as measured by increased cytokine expression these genes could represent additional diseases amenable to immune checkpoint therapy. It was found that loss of MEN1 led to increased PD-L1 expression, as well as upregulated expression of the cytokines CXCL10 and CCL5.

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MEN1 is a TSG encoding the 68kDa protein menin, which has a range of poorly defined functions including an association with homologous-recombination (HR) DNA repair genes, specifically BRCA1, RAD51, and RAD51-AP1. Menin appears to regulate genes through transcriptional regulation but in some cases, such as the stabilisation of FANCD2, also via direct protein binding. MEN1 mutation predisposes to multiple endocrine neoplasia 1 syndrome, characterised by the development of a range of neuroendocrine tumours, and affected patients have limited treatment options.

The biology underpinning MEN1 loss may lead to a tumour environment in the correct state to be targeted by immune checkpoint therapies, potentially in combination with a DNA damaging agent. Immune checkpoint therapies could provide a more effective option for universal treatment of tumours linked to MEN1 loss-of-function.<br><br><i>Thesis embargoed until 31 December 2023</i>.

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Catalogue records · 1

Topics

From keywords
Earth & Environmental Science · Earth & Environmental Science · Earth & Environmental Science · Earth & Environmental Science
Inferred from text
Cancer 65%
Provenance · 4 source records, 9 field assertions
SourceKeyLast seenRaw
ZivaHuboai:figshare.com:article/3263252712 d agoJSON v1
Deakin Research Onlineoai:figshare.com:article/3263252712 d agoJSON v1
DMU Figshareoai:figshare.com:article/3263252712 d agoJSON v1
UCL Research Data Repositoryoai:figshare.com:article/3263252711 d agoJSON v1
FieldAssertionExtractorEvidence
concepts[disease].local:disease:cancerenrichment · zivahub uct ac zakeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:earth-environmentalmapping · zivahub uct ac zaconnector:zivahub_uct_ac_za@1.0.0
concepts[field].local:field:earth-environmentalmapping · dro deakin edu auconnector:dro_deakin_edu_au@1.0.0
concepts[field].local:field:earth-environmentalmapping · figshare dmu ac ukconnector:figshare_dmu_ac_uk@1.0.0
concepts[field].local:field:earth-environmentalmapping · rdr ucl ac ukconnector:rdr_ucl_ac_uk@1.0.0
descriptionsource · zivahub uct ac zaconnector:zivahub_uct_ac_za@1.0.0/metadata/dc/description
license_textsource · zivahub uct ac zaconnector:zivahub_uct_ac_za@1.0.0
publication_datesource · zivahub uct ac zaconnector:zivahub_uct_ac_za@1.0.0
titlesource · zivahub uct ac zaconnector:zivahub_uct_ac_za@1.0.0/metadata/dc/title