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

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

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

journal contribution

posted on 2020-10-21, 13:32 authored by 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 SP Poh, Xin Wang, Stefan Fröhling, Katja 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

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.