Harnessing p53 for targeted cancer therapy: new advances and future directions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00144660" target="_blank" >RIV/00216224:14110/25:00144660 - isvavai.cz</a>
Result on the web
<a href="https://www.tandfonline.com/doi/full/10.1080/21541264.2025.2452711" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/21541264.2025.2452711</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/21541264.2025.2452711" target="_blank" >10.1080/21541264.2025.2452711</a>
Alternative languages
Result language
angličtina
Original language name
Harnessing p53 for targeted cancer therapy: new advances and future directions
Original language description
The transcription factor p53 is the most frequently impaired tumor suppressor in human cancers. In response to various stress stimuli, p53 activates transcription of genes that mediate its tumor-suppressive functions. Distinctive characteristics of p53 outlined here enable a well-defined program of genes involved in cell cycle arrest, apoptosis, senescence, differentiation, metabolism, autophagy, DNA repair, anti-viral response, and anti-metastatic functions, as well as facilitating autoregulation within the p53 network. This versatile, anti-cancer network governed chiefly by a single protein represents an immense opportunity for targeted cancer treatment, since about half of human tumors retain unmutated p53. During the last two decades, numerous compounds have been developed to block the interaction of p53 with the main negative regulator MDM2. However, small molecule inhibitors of MDM2 only induce a therapeutically desirable apoptotic response in a limited number of cancer types. Moreover, clinical trials of the MDM2 inhibitors as monotherapies have not met expectations and have revealed hematological toxicity as a characteristic adverse effect across this drug class. Currently, combination treatments are the leading strategy for enhancing efficacy and reducing adverse effects of MDM2 inhibitors. This review summarizes efforts to identify and test therapeutics that work synergistically with MDM2 inhibitors. Two main types of drugs have emerged among compounds used in the following combination treatments: first, modulators of the p53-regulated transcriptome (including chromatin modifiers), translatome, and proteome, and second, drugs targeting the downstream pathways such as apoptosis, cell cycle arrest, DNA repair, metabolic stress response, immune response, ferroptosis, and growth factor signaling. Here, we review the current literature in this field, while also highlighting overarching principles that could guide target selection in future combination treatments.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA25-18368S" target="_blank" >GA25-18368S: Empowering the p53 to trigger cell death in tumors</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
TRANSCRIPTION-AUSTIN
ISSN
2154-1264
e-ISSN
2154-1272
Volume of the periodical
16
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
44
Pages from-to
3-46
UT code for WoS article
001435684900001
EID of the result in the Scopus database
2-s2.0-86000260484