MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
AuthorMunkhbaatar, E; Dietzen, M; Agrawal, D; Anton, M; Jesinghaus, M; Boxberg, M; Pfarr, N; Bidola, P; Uhrig, S; Hoeckendorf, U; ...
Source TitleNature Communications
University of Melbourne Author/sStrasser, Andreas
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsMunkhbaatar, E., Dietzen, M., Agrawal, D., Anton, M., Jesinghaus, M., Boxberg, M., Pfarr, N., Bidola, P., Uhrig, S., Hoeckendorf, U., Meinhardt, A. -L., Wahida, A., Heid, I., Braren, R., Mishra, R., Warth, A., Muley, T., Poh, P. S. P., Wang, X. ,... 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.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484793
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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