The identification of the NFκB signaling pathway as an epigenetic modulator of tumor behavior and resistance Oligomycin A structure to chemotherapy further improved our knowledge in the intricate molecular

mechanism of HNSCC and further clarified our understanding of the NFκB signaling pathway[216]. Novel therapeutic strategies can now be developed that target epigenetic alterations driven by histone modifications, and the NFκB signaling may serve as an ideal coadjuvant target for therapy. The development of personalized therapies specific for tumor subtypes, in this case tumors with active NFκB signaling, holds the promise of preventing tumor resistance and sensitizing tumors to chemotherapy. Recent advances in genome sequencing, including next-generation sequencing (NGS), have also improved our understanding of altered molecular signaling in HNSCC. NGS was used to identify single-base changes and larger structural variants characterized by insertions, deletions, translocations and viral insertions in HNSCC[3,226].

Interestingly, NGS also revealed that HNSCC have a significant number of mutations in histones, histone modifiers, transcriptional activators and coactivators, and transcription regulators, further emphasizing the complexity of tumor signaling[30]. Collectively, emerging knowledge about tumor behavior and how it correlates with dynamic changes in gene expression mediated by epigenetic events have substantially clarified the concept that successful therapeutic strategies will require targeting of both genetic and epigenetic pathways. ACKNOWLEDGMENTS We thank Dr. Luciana Almeida Oliveira for the CSC images used to illustrate Figure ​Figure44. Footnotes P- Reviewer:

Chen LY, Holan V S- Editor: Tian YL L- Editor: A E- Editor: Lu YJ Supported by University of Michigan, School of Dentistry startup
Core tip: Mesenchymal stem cells (MSCs) may have an important therapeutic potential in acute kidney injury management. A body of evidence has demonstrated that MSCs Dacomitinib act through a paracrine/endocrine secretion of soluble factors and microvesicles. We summarize preclinical studies and ongoing clinical trials that evaluate the role of MSCs in restoring kidney function. We critically explain the current concerns about the use of MSCs and microvesicles that limit their applications in clinical trials. Then, we propose the future directions that could lead to extend MSCs use in humans. INTRODUCTION Acute kidney injury (AKI) is a complex clinical syndrome that affects up to 20% of hospitalized patients. Ischemia/reperfusion injury (IRI) is a major cause of AKI, and it is characterized by acute tubular injury and rapid renal dysfunction, generally caused by ischemic or toxic insults[1-3].