title: Targeting transcription factors: promising new strategies for cancer therapy.
abstract: OBJECTIVE
  A lack of effective treatments for advanced cancer remains a major challenge in oncology. Because cancer is a disease associated with aberrant gene expression patterns, transcription factors, which serve as the convergence points of oncogenic signaling and are functionally altered in many cancers, hold great therapeutic promise.
  
  
  RESULTS
  Many human cancers are dependent on the inappropriate activity of oncogenic transcription factors. By contrast, normal cells can often tolerate disruption of these proteins with little toxicity. Direct inhibition of transcription factor expression (e.g., with RNA interference or microRNAs) and DNA binding (e.g., with oligodeoxynucleotide decoys or pyrrole-imidazole polyamides) has demonstrated antitumor responses with minimal side-effects. New strategies of targeting transcription factors include disrupting critical protein-protein interactions, and restricting binding at the epigenetic level by modulating chromatin accessibility. Moreover, targeting transcription factors in tumor-associated immune cells has the potential to overcome tumor immunoresistance.
  
  
  CONCLUSIONS
  Transcription factors are an important target for cancer therapy, both through direct anticancer effects and immunomodulatory actions. Newly developed delivery systems that specifically target tumor cells also create opportunities for successes in targeting transcription in cancer.
authors.affiliation: aDepartment of Medical Oncology, Dana-Farber Cancer Institute, and Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA bDepartment of Immunology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Yeh
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Toniolo
authors.forename: David A
authors.initials: DA
authors.lastname: Frank
mesh_terms: D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000276:immunology; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018390:Gene Targeting / Q000379:methods* / Q000639:trends; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000276:immunology / Q000627:therapeutic use*; D051881:Receptor, Notch1 / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000627:therapeutic use; D014157:Transcription Factors / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016328:NF-kappa B; C497761:NOTCH1 protein, human; C478985:PDRG1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors