title: p53 abnormalities and potential therapeutic targeting in multiple myeloma.
abstract: p53 abnormalities are regarded as an independent prognostic marker in multiple myeloma. Patients harbouring this genetic anomaly are commonly resistant to standard therapy. Thus, various p53 reactivating agents have been developed in order to restore its tumour suppressive abilities. Small molecular compounds, especially, have gained popularity in its efficacy against myeloma cells. For instance, promising preclinical results have steered both nutlin-3 and PRIMA-1 into phase I/II clinical trials. This review summarizes different modes of p53 inactivation in myeloma and highlights the current p53-based therapies that are being utilized in the clinic. Finally, we discuss the potential and promise that the novel small molecules possess for clinical application in improving the treatment outcome of myeloma.
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077 ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599.
authors.forename: P J
authors.initials: PJ
authors.lastname: Teoh
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077 ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599.
authors.forename: W J
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C446290:PRIMA1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53