MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
- Author(s)
- Munkhbaatar, E; Dietzen, M; Agrawal, D; Anton, M; Jesinghaus, M; Boxberg, M; Pfarr, N; Bidola, P; Uhrig, S; Hockendorf, U; Meinhardt, AL; Wahida, A; Heid, I; Braren, R; Mishra, R; Warth, A; Muley, T; Poh, PSP; Wang, X; Frohling, S; Steiger, K; Slotta-Huspenina, J; van Griensven, M; Pfeiffer, F; Lange, S; Rad, R; Spella, M; Stathopoulos, GT; Ruland, J; Bassermann, F; Weichert, W; Strasser, A; Branca, C; Heikenwalder, M; Swanton, C; McGranahan, N; Jost, PJ;
- Details
- Publication Year 2020-09-10,Volume 11,Issue #1,Page 4527
- Journal Title
- Nature Communications
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NPG
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 32913197
- Publisher's Version
- https://doi.org/10.1038/s41467-020-18372-1
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-020-18372-1- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-10-02 10:28:02
Last Modified: 2020-10-02 10:36:02