Critical review about MDM2 in cancer: Possible role in malignant mesothelioma and implications for treatment

Loredana Urso, Fiorella Calabrese, Adolfo Favaretto, PierFranco Conte, Giulia Pasello

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)220-230
Number of pages11
JournalCritical Reviews in Oncology/Hematology
Volume97
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • Apoptosis
  • MDM2
  • Mesothelioma
  • Neoangiogenesis
  • P53

ASJC Scopus subject areas

  • Oncology
  • Hematology
  • Geriatrics and Gerontology

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