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.
Preview |
Text
McGranahan_s41467-020-18372-1.pdf - Published Version Download (3MB) | Preview |
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 |
Archive Staff Only
 |
View Item |
