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MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically

Munkhbaatar, E; Dietzen, M; Agrawal, D; Anton, M; Jesinghaus, M; Boxberg, M; Pfarr, N; ... Jost, PJ; + view all (2020) MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically. Nature Communications , 11 (1) , Article 4527. 10.1038/s41467-020-18372-1. Green open access

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Abstract

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

Type: Article
Title: MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-020-18372-1
Publisher version: https://doi.org/10.1038/s41467-020-18372-1
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Non-small-cell lung cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10110180
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