Introduction: Specificity protein (Sp) transcription factors (TFs) are members of the Sp/Kruppel-like factor family, and Sp proteins play an important role in embryonic and early postnatal development. Sp1 has been the most extensively investigated member of this family, and expression of this protein decreases with age, whereas Sp1 and other family members (Sp3 and Sp4) are highly expressed in tumors and cancer cell lines.
Area covered: The prognostic significance of Sp1 in cancer patients and the functional pro-oncogenic activities of Sp1, Sp3 and Sp4 in cancer cell lines are summarized. Several different approaches have been used to target downregulation of Sp TFs and Sp-regulated genes, and this includes identification of different structural classes of antineoplastic agents including NSAIDs, natural products and their synthetic analogs and several well-characterized drugs including arsenic trioxide, aspirin and metformin. The multiple pathways involved in drug-induced Sp downregulation are also discussed.
Expert opinion: The recognition by the scientific and clinical community that experimental and clinically used antineoplastic agents downregulate Sp1, Sp3 and Sp4, and pro-oncogenic Sp-regulated genes will facilitate future clinical applications for individual drug and drug combination therapies that take advantage of their unusual effects.
Keywords: Kruppel-like factor family; antineoplastic agents; specificity protein transcription factors; targeted therapy.