title: Synthetic lethal screens as a means to understand and treat MYC-driven cancers.
abstract: Although therapeutics against MYC could potentially be used against a wide range of human cancers, MYC-targeted therapies have proven difficult to develop. The convergence of breakthroughs in human genomics and in gene silencing using RNA interference (RNAi) have recently allowed functional interrogation of the genome and systematic identification of synthetic lethal interactions with hyperactive MYC. Here, we focus on the pathways that have emerged through RNAi screens and present evidence that a subset of genes showing synthetic lethality with MYC are significantly interconnected and linked to chromatin and transcriptional processes, as well as to DNA repair and cell cycle checkpoints. Other synthetic lethal interactions with MYC point to novel pathways and potentially broaden the repertoire of targeted therapies. The elucidation of MYC synthetic lethal interactions is still in its infancy, and how these interactions may be influenced by tissue-specific programs and by concurrent genetic change will require further investigation. Nevertheless, we predict that these studies may lead the way to novel therapeutic approaches and new insights into the role of MYC in cancer.
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cermelli
authors.forename: In Sock
authors.initials: IS
authors.lastname: Jang
authors.forename: Brady
authors.initials: B
authors.lastname: Bernard
authors.forename: Carla
authors.initials: C
authors.lastname: Grandori
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology; D049108:Cell Enlargement; D004260:DNA Repair / Q000235:genetics; D005544:Forecasting; D005804:Genes, Lethal / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D016259:Genes, myc / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering