TY - JOUR
T1 - Critical review about MDM2 in cancer
T2 - Possible role in malignant mesothelioma and implications for treatment
AU - Urso, Loredana
AU - Calabrese, Fiorella
AU - Favaretto, Adolfo
AU - Conte, PierFranco
AU - Pasello, Giulia
PY - 2016/1/1
Y1 - 2016/1/1
N2 - The tumor suppressor p53 regulates genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis and senescence. p53 is mutated in about 50% of the human cancers, while in tumors with wild-type p53 gene, the protein function may be lost because of overexpression of Murine Double Minute 2 (MDM2). MDM2 targets p53 for ubiquitylation and proteasomal degradation. p53 reactivation through MDM2 inhibitors seems to be a promising strategy to sensitize p53 wild-type cancer cells to apoptosis. Moreover, additional p53-independent molecular functions of MDM2, such as neoangiogenesis promotion, have been suggested. Thus, MDM2 might be a target for anticancer treatment because of its antiapoptotic and proangiogenetic role. Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor where wild-type p53 might be present. The present review gives a complete landscape about the role of MDM2 in cancer pathogenesis, prognosis and treatment, with particular focus on Malignant Pleural Mesothelioma.
AB - The tumor suppressor p53 regulates genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis and senescence. p53 is mutated in about 50% of the human cancers, while in tumors with wild-type p53 gene, the protein function may be lost because of overexpression of Murine Double Minute 2 (MDM2). MDM2 targets p53 for ubiquitylation and proteasomal degradation. p53 reactivation through MDM2 inhibitors seems to be a promising strategy to sensitize p53 wild-type cancer cells to apoptosis. Moreover, additional p53-independent molecular functions of MDM2, such as neoangiogenesis promotion, have been suggested. Thus, MDM2 might be a target for anticancer treatment because of its antiapoptotic and proangiogenetic role. Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor where wild-type p53 might be present. The present review gives a complete landscape about the role of MDM2 in cancer pathogenesis, prognosis and treatment, with particular focus on Malignant Pleural Mesothelioma.
KW - Apoptosis
KW - MDM2
KW - Mesothelioma
KW - Neoangiogenesis
KW - P53
UR - http://www.scopus.com/inward/record.url?scp=84952637494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952637494&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2015.08.019
DO - 10.1016/j.critrevonc.2015.08.019
M3 - Article
AN - SCOPUS:84952637494
VL - 97
SP - 220
EP - 230
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
SN - 1040-8428
ER -