EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools
| Autor: | Mark C. Howell Jr., Ryan Green, Junior Cianne, Guy W. Dayhoff, Vladimir N. Uversky, Shyam Mohapatra, Subhra Mohapatra |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. :1-20 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | Epidermal Growth Factor Receptor (EGFR) signaling and EGFR mutations play key roles in cancer pathogenesis, particularly in the development of drug resistance. For the ∼20% of all non-small cell lung cancer (NSCLC) patients that harbor an activating mutation, EGFR tyrosine kinase inhibitors (TKIs) provide initial clinical responses. However, long-term efficacy is not possible due to acquired drug resistance. Despite a gradually increasing knowledge of the mechanisms underpinning the development of resistance in tumors, there has been very little success in overcoming it and it is probable that many additional mechanisms are still unknown. Herein, publicly available RNASeq (RNA sequencing) datasets comparing lung cancer cell lines treated with EGFR TKIs until resistance developed with their corresponding parental cells and protein array data from our own EGFR TKI treated xenograft tumors, were analyzed for differential gene expression, with the intent to investigate the potential mechanisms of drug resistance to EGFR TKIs. Pathway analysis, as well as structural disorder analysis of proteins in these pathways, revealed several key proteins, including DUSP1, DUSP6, GAB2, and FOS, that could be targeted using novel combination therapies to overcome EGFR TKI resistance in lung cancer.Communicated by Ramaswamy H. Sarma. |
| Databáze: | OpenAIRE |
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