Targeting transcription factors for cancer therapy

Abstract

Despite all of the advances in understanding the operations of cancer cells, cancer is on track to pass heart disease as the leading cause of death in the developed world. The primary treatment approach for advanced cancer remains chemotherapeutic drugs that kill cells, both normal and malignant, in a relatively indiscriminate manner. One recent advance in treatment has been the introduction of drugs that target kinases, which can undergo mutations and become activated inappropriately in cancer cells. However, the maximal benefit that can derive from this approach may soon be reached, and a clear need exists for identifying other therapeutic targets that will have broader applicability. Transcription factors, proteins that regulate the expression of genes within a cell and ultimately control cell behavior, are frequently locked in an 'on' position in cancer cells; when the transcription factors are shut off, a cancer cell will generally stop growing or begin to die. In contrast, normal cells tolerate a loss of transcription factor function with little consequence, as a result of redundancies that are present under normal conditions. Despite challenges involved in developing drugs to target transcription factors, increasing evidence indicates that this approach may be a highly promising strategy in the development of cancer treatments that are more effective and less toxic than existing options.