Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Munkhbaatar, E; Dietzen, M; Agrawal, D; Anton, M; Jesinghaus, M; Boxberg, M; Pfarr, N; Bidola, P; Uhrig, S; Höckendorf, U; Meinhardt, AL; Wahida, A; Heid, I; Braren, R; Mishra, R; Warth, A; Muley, T; Poh, PSP; Wang, X; Fröhling, 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.
MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
Nat Commun. 2020; 11(1):4527
Doi: 10.1038/s41467-020-18372-1
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- Führende Autor*innen der Med Uni Graz
- Jost Philipp
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Antineoplastic Agents - pharmacology, therapeutic use
- Apoptosis - drug effects, genetics
- Carcinoma, Non-Small-Cell Lung - diagnostic imaging, drug therapy, genetics, pathology
- Cell Line, Tumor - administration & dosage
- Cell Survival - drug effects, genetics
- Clonal Evolution - administration & dosage
- DNA Copy Number Variations - administration & dosage
- Datasets as Topic - administration & dosage
- Disease Models, Animal - administration & dosage
- Disease Progression - administration & dosage
- Humans - administration & dosage
- Lung - diagnostic imaging, pathology
- Lung Neoplasms - diagnostic imaging, drug therapy, genetics, pathology
- Mice - administration & dosage
- Mice, Transgenic - administration & dosage
- Mutation - administration & dosage
- Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors, genetics
- Primary Cell Culture - administration & dosage
- Prospective Studies - administration & dosage
- Proto-Oncogene Proteins p21(ras) - genetics
- Pyrimidines - pharmacology, therapeutic use
- RNA-Seq - administration & dosage
- Retrospective Studies - administration & dosage
- Spheroids, Cellular - administration & dosage
- Thiophenes - pharmacology, therapeutic use
- Tumor Burden - drug effects, genetics
- Tumor Suppressor Protein p53 - genetics
- X-Ray Microtomography - administration & dosage