Insights into the multi-faceted role of Pioneer transcription factors in glioma formation and progression with targeting options

Pioneer transcription factors (TFs) present an important subtype of transcription factors which are vital for cell programming during embryonic development and cellular memory during mitotic growth, as well as cell fate reprogramming. Pioneer TFs can engage specific target binding sites on nucleosomal DNA to attract chromatin remodeling complexes, cofactors, and other transcription factors, ultimately controlling gene expression by shaping locally the epigenome. The priority of binding that they exhibit in contrast to other transcription factors and their involvement in crucial events regarding cell fate, has implicated their aberrant function in the pathogenesis of several disorders including carcinogenesis. Emerging experimental data indicate that certain Pioneer TFs are highly implicated in gliomas development, in neoplastic cell proliferation, angiogenic processes, resistance to therapy, and patient survival. Herein, we describe the main structural characteristics and functional mechanisms of pioneer TFs, focusing on their central role in the pathogenesis and progression of gliomas. We further highlight the current treatment options ranging from natural agents (oleanolic acid) to a variety of chemical compounds (APR-246, COTI-2) and discuss potential delivery systems, including nanoparticles, viral vectors, and intracellular protein delivery techniques.