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

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

Nature communications (2020-09-12)

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 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

PMID32913197

RESUMEN

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.

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MABS194

Sigma-Aldrich

Anti-c-K-Ras Antibody, clone 234-4.2, clone 234-4.2, from mouse