C URRENT OPINION Targeting transcription factors: promising new strategies for cancer therapy

TLDR: Transcription factors are an important target for cancer therapy, both through direct anticancer effects and immunomodulatory actions, and newly developed delivery systems that specifically target tumor cells also create opportunities for successes in targeting transcription in cancer.

Abstract: Purpose of reviewA lack of effective treatments for advanced cancer remains a major challenge in oncology. Because canceris a disease associated with aberrant gene expression patterns, transcription factors, which serve as theconvergence points of oncogenic signaling and are functionally altered in many cancers, hold greattherapeutic promise.Recent findingsMany human cancers are dependent on the inappropriate activity of oncogenic transcription factors. Bycontrast, normal cells can often tolerate disruption of these proteins with little toxicity. Direct inhibition oftranscription factor expression (e.g., with RNA interference or microRNAs) and DNA binding (e.g., witholigodeoxynucleotide decoys or pyrrole-imidazole polyamides) has demonstrated antitumor responses withminimal 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 overcometumor immunoresistance.SummaryTranscription factors are an important target for cancer therapy, both through direct anticancer effects andimmunomodulatory actions. Newly developed delivery systems that specifically target tumor cells alsocreate opportunities for successes in targeting transcription in cancer.Keywordscancer, therapy, transcription factor