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Understanding cancer drug resistance with Sleeping Beauty functional genomic screens: application to MAPK inhibition in cutaneous melanoma

ABSTRACT: Understanding cancer drug resistance with Sleeping Beauty functional genomic screens: application to MAPK inhibition in cutaneous melanoma

PROVIDER: PRJNA941076 | ENA |

REPOSITORIES: ENA

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Sleeping Beauty Expression data from mouse

Project description:We extracted RNA of 39 mouse tissue of various genotypes and performed expression microarrays. Subsequently a screen was conducted using the Sleeping Beauty (SB) transposon to identify breast cancer candidate genes. 39 mouse samples expression data.

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Understanding cancer drug resistance with Sleeping Beauty functional genomic screens: application to MAPK inhibition in cutaneous melanoma

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Sleeping Beauty Expression data from mouse

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Understanding cancer drug resistance with <i>Sleeping Beauty</i> functional genomic screens: Application to MAPK inhibition in cutaneous melanoma.

Project description:Combined BRAF and MEK inhibition is an effective treatment for BRAF-mutant cutaneous melanoma. However, most patients progress on this treatment due to drug resistance. Here, we applied the Sleeping Beauty transposon system to understand how melanoma evades MAPK inhibition. We found that the specific drug resistance mechanisms differed across melanomas in our genetic screens of five cutaneous melanoma cell lines. While drivers that reactivated MAPK were highly conserved, many others were cell-line specific. One such driver, VAV1, activated a de-differentiated transcriptional program like that of hyperactive RAC1, RAC1P29S. To target this mechanism, we showed that an inhibitor of SRC, saracatinib, blunts the VAV1-induced transcriptional reprogramming. Overall, we highlighted the importance of accounting for melanoma heterogeneity in treating cutaneous melanoma with MAPK inhibitors. Moreover, we demonstrated the utility of the Sleeping Beauty transposon system in understanding cancer drug resistance.

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Therapeutic immune cell engineering with an mRNA : AAV-Sleeping Beauty composite system [Splinkerette]

Project description:We evaluated the insertion site profile of the MAJESTIC (mRNA : AAV-Sleeping Beauty) CAR generation method.

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Identification of genes involved in SHH subgroup medulloblastoma using murine whole-body Sleeping Beauty insertional mutagenesis

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Identification of genes involved in SHH subgroup medulloblastoma using murine whole-body Sleeping Beauty insertional mutagenesis

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2013-07-09 | E-GEOD-43994 | biostudies-arrayexpress

Long-Term Follow-up Study of Subjects Treated With Autologous T Cells Using the Sleeping Beauty System to Express TCRs

Project description:Long-Term Follow-Up Study for Subjects Enrolled in the Phase I/II Study of Autologous T Cells Engineered using the Sleeping Beauty System to Express T cell Receptors (TCRs) Reactive Against Cancer-specific Mutations in Subjects with Solid Tumors

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