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, Bidola P, Uhrig S, Hoeckendorf U, Meinhardt AL, Wahida A, Heid I, Braren R, Mishra R, Warth A, Muley T, Poh PSP, Wang X, Froehling S, Steiger K, Slotta-Huspenina J, Van Griensven M, Pfeiffer F, Lange S, Rad R, Spella M, Stathopoulos GT, Ruland J, Bassermann F, Weichert W, Strasser A, Branca C, Heikenwalder M, Swanton C, Mcgranahan N, Jost PJ (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 11

Article Number: 4527

Journal Issue: 1

DOI: 10.1038/s41467-020-18372-1

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.

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) University College London (UCL) GB United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg DE Germany (DE) Maastricht University NL Netherlands (NL) University of Patras (UPATRAS) GR Greece (GR) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Walter and Eliza Hall Institute of Medical Research (WEHI) AU Australia (AU)

How to cite

APA:

Munkhbaatar, E., Dietzen, M., Agrawal, D., Anton, M., Jesinghaus, M., Boxberg, M.,... Jost, P.J. (2020). MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-18372-1

MLA:

Munkhbaatar, Enkhtsetseg, et al. "MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically." Nature Communications 11.1 (2020).

BibTeX: Download