MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition
Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low “variant” subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which combined with chemotherapy strongly suppresses tumor progression and increases survival. These data identify molecular features for patient stratification and uncover a novel targeted treatment approach for MYC-driven SCLC.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
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EGAD00001003099 | Illumina HiSeq 2000 | 14 |
Publications | Citations |
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MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition.
Cancer Cell 31: 2017 270-285 |
316 |
MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer.
Nat Commun 10: 2019 3485 |
40 |
Ferroptosis response segregates small cell lung cancer (SCLC) neuroendocrine subtypes.
Nat Commun 12: 2021 2048 |
65 |
Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer.
Theranostics 13: 2023 2384-2407 |
11 |