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

Enkhtsetseg Munkhbaatar, Michelle Dietzen, Deepti Agrawal, Martina Anton, Moritz Jesinghaus, Melanie Boxberg, Nicole Pfarr, Pidassa Bidola, Sebastian Uhrig, Ulrike Höckendorf, Anna-Lena Meinhardt, Adam Wahida, Irina Heid, Rickmer Braren, Ritu Mishra, Arne Warth, Thomas Muley, Patrina S P Poh, Xin Wang, Stefan FröhlingKatja Steiger, Julia Slotta-Huspenina, Martijn van Griensven, Franz Pfeiffer, Sebastian Lange, Roland Rad, Magda Spella, Georgios T Stathopoulos, Jürgen Ruland, Florian Bassermann, Wilko Weichert, Andreas Strasser, Caterina Branca, Mathias Heikenwalder, Charles Swanton, Nicholas McGranahan, Philipp J Jost*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article number4527
Number of pages13
JournalNature Communications
Issue number1
Publication statusPublished - 10 Sep 2020

Cite this