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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 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Jost Philipp

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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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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

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