Reactivating p53 functions by suppressing its novel inhibitor iASPP: a potential therapeutic opportunity in p53 wild-type tumors

What is it about?

Although approximately 50% of all human cancers carry p53 gene mutations, a subset of tumors display defective p53 function, but retain wild-type (WT) p53. Here, we discuss direct and indirect mechanisms leading to the loss of WT p53 activities in human tumors, and focus on the roles of iASPP, a direct inhibitor of WT p53, in promoting proliferation, invasion, drug or radiation-resistance and metastasis. We also address recent works utilizing tumor-suppressor microRNA, peptide and small compounds for iASPP-targeted cancer therapy.

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Why is it important?

Recent findings demonstrate that the overexpression of iASPP is detected in various human cancer types and correlates with enhanced proliferation, aggressive behavior, the resistance to radiation/chemotherapy and worse patient prognosis, and uncover the oncogenic roles of iASPP in promoting tumorigenesis and invasion. From the therapeutic view, we highlight promising perspectives of microRNA-124, peptide and small molecules that reduce or block iASPP for the treatment of cancer. The mechanisms underlying aberrant expression of iASPP in human tumors, how iASPP exerts its oncogenic effects and potential strategies that target iASPP, are all research areas of immense interest. The discoveries shown in this review will provide a basis for new potential therapeutic intervention aiming at suppression of tumor growth, cancer stemness and metastasis, and undoubtedly play an important role in the way we treat WT p53-containing human tumors.