TY - JOUR
T1 - MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
AU - Munkhbaatar, Enkhtsetseg
AU - Dietzen, Michelle
AU - Agrawal, Deepti
AU - Anton, Martina
AU - Jesinghaus, Moritz
AU - Boxberg, Melanie
AU - Pfarr, Nicole
AU - Bidola, Pidassa
AU - Uhrig, Sebastian
AU - Höckendorf, Ulrike
AU - Meinhardt, Anna Lena
AU - Wahida, Adam
AU - Heid, Irina
AU - Braren, Rickmer
AU - Mishra, Ritu
AU - Warth, Arne
AU - Muley, Thomas
AU - Poh, Patrina S.P.
AU - Wang, Xin
AU - Fröhling, Stefan
AU - Steiger, Katja
AU - Slotta-Huspenina, Julia
AU - van Griensven, Martijn
AU - Pfeiffer, Franz
AU - Lange, Sebastian
AU - Rad, Roland
AU - Spella, Magda
AU - Stathopoulos, Georgios T.
AU - Ruland, Jürgen
AU - Bassermann, Florian
AU - Weichert, Wilko
AU - Strasser, Andreas
AU - Branca, Caterina
AU - Heikenwalder, Mathias
AU - Swanton, Charles
AU - McGranahan, Nicholas
AU - Jost, Philipp J.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85090501561&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18372-1
DO - 10.1038/s41467-020-18372-1
M3 - Article
C2 - 32913197
AN - SCOPUS:85090501561
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4527
ER -