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Targeting mutant p53 in cancer: a long road to precision therapy
Author(s) -
Mantovani Fiamma,
Walerych Dawid,
Sal Giannino Del
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13948
Subject(s) - mutant , cancer therapy , cancer , targeted therapy , cancer research , medicine , computational biology , biology , genetics , gene
The TP 53 tumor suppressor is the most frequently mutated gene in human cancers. In recent years, a blooming of research efforts based on both cell lines and mouse models have highlighted how deeply mutant p53 proteins affect fundamental cellular pathways with cancer‐promoting outcomes. Neomorphic mutant p53 activities spread over multiple levels, impinging on chromatin structure, transcriptional regulation and micro RNA maturation, shaping the proteome and the cell's metabolic pathways, and also exerting cytoplasmic functions and displaying cell‐extrinsic effects. These tumorigenic activities are inextricably linked with the blend of highly corrupted processes that characterize the tumor context. Recent studies indicate that successful strategies to extract core aspects of mutant p53 oncogenic potential and to identify unique tumor dependencies entail the superimposition of large‐scale analyses performed in multiple experimental systems, together with a mindful use of animal models. This will hopefully soon lead to the long‐awaited inclusion of mutant p53 as an actionable target of clinical antitumor therapies.

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