Oxygen tension-dependent variability in the cancer cell kinome and response to combination therapies
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1023981 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26283493_1.fastq.gz | Fastqsanger.gz | |||
| SRR26283493_2.fastq.gz | Fastqsanger.gz | |||
| SRR26283494_1.fastq.gz | Fastqsanger.gz | |||
| SRR26283494_2.fastq.gz | Fastqsanger.gz | |||
| SRR26283495_1.fastq.gz | Fastqsanger.gz |
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Project description:Solid tumors are characterized by significantly lower oxygen (O2) levels. Despite this fact, routine preclinical cancer studies are performed under ambient O2 conditions. We have developed an experimental approach that allows us to collect, process and evaluate cancer and non-cancer cells under physioxia (3-5% O2), in such a way that there is very minimal exposure to air. We have shown in previous studies that ambient and physioxic O2 differentially impact relevant cell surface markers and sensitivity to therapy. In this study, our goal was to further explore oxygen-dependent signaling pathway alterations and to determine how these pathways influence response to targeted therapies. Using cells derived from transgenic mouse mammary tumors and healthy primary human breast epithelial cells, we show the impact of ambient air and physioxia on the kinome, with subsequent pathway alterations that mediate the effectiveness of single and combination therapies. Our data emphasize the importance of O2 considerations in preclinical cancer research and drug development.
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