Author Affiliations: Division of Hematology–Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Dr Konstantinopoulos); Department of Biological Chemistry, University of Athens Medical School, Athens, Greece (Drs Konstantinopoulos and Papavassiliou).
In the era of genomic medicine, diseases are perceived as manifestations of abnormal gene expression patterns.1 Cancer is the prime example of this concept. Transcription factors,2 the terminal effectors of the malignant gene expression patterns, occupy a central role in all 6 classic hallmarks of carcinogenesis: self-sufficiency in growth stimuli, insensitivity to antigrowth signals, endless replication, angiogenesis, tissue invasion, and metastasis.3 An ever-increasing number of pathognomonic tumor-specific genetic and epigenetic events have been shown to directly inactivate tumor suppressor or activate oncogenic transcription factors (Table). Alternatively, modulation of transcription factor activity may be the critical consequence of genetic and epigenetic alterations that affect tumor suppressor genes or oncogenes implicated in upstream signal transduction pathways. For example, all distinct chromosomal translocations found in mucosa-associated lymphoid tissue lymphomas culminate in induction of nuclear factor κB (NF-κB) transcriptional activity without individually involving NF-κB directly.
Konstantinopoulos PA, Papavassiliou AG. Seeing the Future of Cancer-Associated Transcription Factor Drug Targets. JAMA. 2011;305(22):2349-2350. doi:10.1001/jama.2011.727