Melanoma Molecular Maps Projects



Title: List of p53 activators
Legend: p53 mutation occurs in over half of all human tumors. Among the remaining tumors (including most melanomas), despite the presence of wild type p53, the pathways of p53 induced cell cycle arrest and apoptosis are deficient, which is due to mechanisms such as MDM2 (HDM2) overexpression or p14 (p14 alternative reading frame, ARF) deficiency. Therefore, restoration of p53 activity represents an appealing approach to molecularly targeted cancer therapy. Besides gene therapy for the introduction of wild-type p53 into tumor cells, another strategy is based on the development of p53 activators, such as nutlins (nutlin-1, nutlin-2, nutlin-3), DW1/2, CP-31392, PRIMA1 and S100 antisense RNA. In the absence of p53 or the presence of mutant p53, p53 family members (e.g. p73), may function instead of p53 in the pathway of tumor suppression: accordingly, p73 activators are also being developed (e.g. NSC143491 [a derivative of daunorubicin, a well known chemotherapeutic anthracycline], NSC254681). REFERENCES: [1] Bourdon JC, Br J Cancer 2007, 97:277-82. [2] Wang W et al, Curr Opin Oncol 2008, 20:90-6
Author: The MMMP Team (updated: Jan 2008)

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