ΔNp63α in cancer: importance and therapeutic opportunities

• Published in: Trends in cell biology Vol. 33; no. 4; pp. 280 - 292
• Main Authors: Fisher, Matthew L., Balinth, Seamus, Mills, Alea A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2023
• Subjects: cancer; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms - genetics; Neoplasms - therapy; p63; Protein Isoforms - genetics; Protein Isoforms - metabolism; signaling; therapeutic strategy; Transcription Factors - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; cancer; signaling; therapeutic strategy; p63
• ISSN: 0962-8924; 1879-3088
• DOI: 10.1016/j.tcb.2022.08.003

Our understanding of cancer and the key pathways that drive cancer survival has expanded rapidly over the past several decades. However, there are still important challenges that continue to impair patient survival, including our inability to target cancer stem cells (CSCs), metastasis, and drug resistance. The transcription factor p63 is a p53 family member with multiple isoforms that carry out a wide array of functions. Here, we discuss the critical importance of the ΔNp63α isoform in cancer and potential therapeutic strategies to target ΔNp63α expression to impair the CSC population, as well as to prevent metastasis and drug resistance to improve patient survival.
ΔNp63α is a p63 isoform in the p53 family that is a master regulator of epithelial stemness in normal tissue.In cancer, ΔNp63α regulates a number of key aspects of cancer progression, including cancer stem cell (CSC) maintenance, metastasis, and drug resistance, through regulation of several downstream pathways.ΔNp63α is difficult to target directly, but multiple pathways upstream of ΔNp63α with druggable targets have been identified that represent potential therapeutic opportunities in cancer.Many pathways upstream of ΔNp63α are involved in crosstalk with the tumor microenvironment. With growing interest in targeting the tumor niche, further investigation into how ΔNp63α is involved in crosstalk with the microenvironment represents an exciting area of future investigation.