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ACGH and high-throughput transcriptome profiling of non-small cell lung cancer cell lines sensitive or resistant to CPL304110 FGFR inhibitor

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189270 | GEO | 2021/11/23

REPOSITORIES: GEO

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aCGH profiling for non-small cell lung cancer cell lines sensitive or resistant to CPL304110 FGFR inhibitor

Project description:FGFR signalling is one of the most prominent pathways involved in cell growth and development, as well as cancer progression. FGFR1 amplification occurs in approximately 20% of all squamous cell lung carcinomas (SCC) - one of the most common subtypes of non-small cell lung carcinoma (NSCLC), indicating FGFR as a potential target for the new anti-cancer therapies. However, acquired resistance to this type of therapies remains a clinical issue. Here, we investigated the NSCLC cell lines response and potential mechanism of acquired resistance to novel selective FGFR inhibitor CPL304110. We found that despite significant genomic differences between CPL304110-sensitive cell lines, their resistant variants were characterized by upregulated p38 expression/phosphorylation, as well as enhanced expression of genes involved in MAPK signalling. We revealed that p38 inhibition restored sensitivity to CPL304110 in these cells. Moreover, overexpression of this kinase in parental cells led to impaired response to FGFR inhibition, thus confirming that p38 MAPK is a driver of resistance to a novel FGFR inhibitor. Taken together, our results provide an insight into the potential direction for NSCLC targeted therapy.

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High-throughput transcriptome profiling of non-small cell lung cancer cell lines sensitive or resistant to CPL304110 FGFR inhibitor

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