The role of p53 in cancer drug resistance and targeted chemotherapy

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000393295500148&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.18632/oncotarget.13475
eISSN
1949-2553
Externe Identifier
  • Clarivate Analytics Document Solution ID: EJ5YP
  • PubMed Identifier: 27888811
Ausgabe der Veröffentlichung
5
Zeitschrift
ONCOTARGET
Schlüsselwörter
  • cytotoxic chemotherapy
  • drug resistance
  • medicinal chemistry
  • prognostic factors
  • targeted chemotherapy
Paginierung
8921 - 8946
Datum der Veröffentlichung
2017
Status
Published
Titel
The role of p53 in cancer drug resistance and targeted chemotherapy
Sub types
  • Review
Ausgabe der Zeitschrift
8

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
DOI
10.18632/oncotarget.13475
eISSN
1949-2553
Ausgabe der Veröffentlichung
5
Zeitschrift
Oncotarget
Sprache
en
Online publication date
2016
Paginierung
8921 - 8946
Datum der Veröffentlichung
2017
Status
Published
Herausgeber
Impact Journals, LLC
Herausgeber URL
http://dx.doi.org/10.18632/oncotarget.13475
Datum der Datenerfassung
2020
Titel
The role of p53 in cancer drug resistance and targeted chemotherapy
Ausgabe der Zeitschrift
8

Datenquelle: Crossref

Abstract
Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab). Such mutations in the TP53 gene are often accompanied by changes in the conformation of the p53 protein. Small molecules that restore the wild-type conformation of p53 and, consequently, rebuild its proper function have been identified. These promising agents include PRIMA-1, MIRA-1, and several derivatives of the thiosemicarbazone family. In addition to mutations in p53 itself, p53 activity may be also be impaired due to alterations in p53's regulating proteins such as MDM2. MDM2 functions as primary cellular p53 inhibitor and deregulation of the MDM2/p53-balance has serious consequences. MDM2 alterations often result in its overexpression and therefore promote inhibition of p53 activity. To deal with this problem, a judicious approach is to employ MDM2 inhibitors. Several promising MDM2 inhibitors have been described such as nutlins, benzodiazepinediones or spiro-oxindoles as well as novel compound classes such as xanthone derivatives and trisubstituted aminothiophenes. Furthermore, even naturally derived inhibitor compounds such as α-mangostin, gambogic acid and siladenoserinols have been discovered. In this review, we discuss in detail such small molecules that play a pertinent role in affecting the p53-MDM2 signaling axis and analyze their potential as cancer chemotherapeutics.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.18632/oncotarget.13475
eISSN
1949-2553
Externe Identifier
  • PubMed Identifier: 27888811
  • PubMed Central ID: PMC5352454
Open access
true
ISSN
1949-2553
Ausgabe der Veröffentlichung
5
Zeitschrift
Oncotarget
Schlüsselwörter
  • Animals
  • Humans
  • Neoplasms
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Gene Expression Regulation, Neoplastic
  • Protein Conformation
  • Structure-Activity Relationship
  • Drug Resistance, Neoplasm
  • Mutation
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-mdm2
  • Molecular Targeted Therapy
Sprache
eng
Medium
Print
Open access status
Open Access
Paginierung
8921 - 8946
Datum der Veröffentlichung
2017
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2016
Titel
The role of p53 in cancer drug resistance and targeted chemotherapy.
Sub types
  • review-article
  • Review
  • Journal Article
Ausgabe der Zeitschrift
8

Files

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=13475&path%5B%5D=42738 https://europepmc.org/articles/PMC5352454?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab). Such mutations in the TP53 gene are often accompanied by changes in the conformation of the p53 protein. Small molecules that restore the wild-type conformation of p53 and, consequently, rebuild its proper function have been identified. These promising agents include PRIMA-1, MIRA-1, and several derivatives of the thiosemicarbazone family. In addition to mutations in p53 itself, p53 activity may be also be impaired due to alterations in p53's regulating proteins such as MDM2. MDM2 functions as primary cellular p53 inhibitor and deregulation of the MDM2/p53-balance has serious consequences. MDM2 alterations often result in its overexpression and therefore promote inhibition of p53 activity. To deal with this problem, a judicious approach is to employ MDM2 inhibitors. Several promising MDM2 inhibitors have been described such as nutlins, benzodiazepinediones or spiro-oxindoles as well as novel compound classes such as xanthone derivatives and trisubstituted aminothiophenes. Furthermore, even naturally derived inhibitor compounds such as α-mangostin, gambogic acid and siladenoserinols have been discovered. In this review, we discuss in detail such small molecules that play a pertinent role in affecting the p53-MDM2 signaling axis and analyze their potential as cancer chemotherapeutics.
Date of acceptance
2016
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/27888811
DOI
10.18632/oncotarget.13475
eISSN
1949-2553
Externe Identifier
  • PubMed Central ID: PMC5352454
Ausgabe der Veröffentlichung
5
Zeitschrift
Oncotarget
Schlüsselwörter
  • cytotoxic chemotherapy
  • drug resistance
  • medicinal chemistry
  • prognostic factors
  • targeted chemotherapy
  • Animals
  • Antineoplastic Agents
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms
  • Protein Conformation
  • Proto-Oncogene Proteins c-mdm2
  • Structure-Activity Relationship
  • Tumor Suppressor Protein p53
Sprache
eng
Country
United States
Paginierung
8921 - 8946
PII
13475
Datum der Veröffentlichung
2017
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2018
Titel
The role of p53 in cancer drug resistance and targeted chemotherapy.
Sub types
  • Journal Article
  • Review
Ausgabe der Zeitschrift
8

Datenquelle: PubMed

Beziehungen:
Eigentum von

Werkzeuge