Abstract: Methods are provided for treating a subject having a MYC-driven neoplasia. Aspects of the methods include administering to the subject an amount of an inhibitor of a target gene effective to treat the subject for the MYC-driven neoplasia. Methods are also provided for identifying a MYC-dependent target gene in a MYC-driven neoplasia. Aspects of the method include identifying the MYC-dependent target gene based on a phenotype detected in a first tumor cell line conditionally expressing MYC that is absent or quantitatively different in a second tumor cell line conditionally repressing MYC when the two cell lines are contacted with a CRISPR-based gene silencing agent. Kits and cell lines for practicing the methods of the disclosure are also provided.

Abstract: Provided are methods of enhancing immunogenicity of cancers. In certain aspects, the methods include administering an effective amount of a sialic acid modulator to an individual identified as having a cancer comprising dysregulated Myc. According to some aspects, the methods include administering an effective amount of a disialyl-T modulator to an individual identified as having a cancer comprising cell surface expression of disialyl-T. In certain aspects, the methods include administering an effective amount of an agent to an individual identified as having a cancer comprising cell surface expression of a glycoprotein comprising an O-glycosylated mucin-like domain, where the agent modulates the glycoprotein. Also provided are methods of assessing whether a cancer of an individual comprises dysregulated Myc.

Abstract: Methods are provided for treating a subject having a MYC-driven neoplasia. Aspects of the methods include administering to the subject an amount of an inhibitor of a target gene effective to treat the subject for the MYC-driven neoplasia. Methods are also provided for identifying a MYC-dependent target gene in a MYC-driven neoplasia. Aspects of the method include identifying the MYC-dependent target gene based on a phenotype detected in a first tumor cell line conditionally expressing MYC that is absent or quantitatively different in a second tumor cell line conditionally repressing MYC when the two cell lines are contacted with a CRISPR-based gene silencing agent. Kits and cell lines for practicing the methods of the disclosure are also provided.

Abstract: Provided are MYC-reporters and MYC-reporter expression vectors having MYC-reporter activity. Also provided are cells containing MYC-reporters and/or MYC-reporter expression vectors as well as animals containing such cells and/or genetically modified to contain one or more MYC-reporters and/or expression vectors. Also provided are methods of screening, including methods of screening a candidate agent for MYC repression. The subject methods may, in some instances, employ one or more of the provided MYC-reporters, expression vectors, cells and/or transgenic animals.