| Resistance and gain-of-resistance phenotypes in cancers harboring wild-type p53. | |
| | |
MedLine Citation:
|
PMID: 22227014 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Chemotherapy is the bedrock for the clinical management of cancer, and the tumor suppressor p53 has a central role in this therapeutic modality. This protein facilitates favorable antitumor drug response through a variety of key cellular functions, including cell cycle arrest, senescence, and apoptosis. These functions essentially cease once p53 becomes mutated, as occurs in ∼50% of cancers, and some p53 mutants even exhibit gain-of-function effects, which lead to greater drug resistance. However, it is becoming increasingly evident that resistance is also seen in cancers harboring wild-type p53. In this review, we discuss how wild-type p53 is inactivated to render cells resistant to antitumor drugs. This may occur through various mechanisms, including an increase in proteasomal degradation, defects in post-translational modification, and downstream defects in p53 target genes. We also consider evidence that the resistance seen in wild-type p53 cancers can be substantially greater than that seen in mutant p53 cancers, and this poses a far greater challenge for efforts to design strategies that increase drug response in resistant cancers already primed with wild-type p53. Because the mechanisms contributing to this wild-type p53 "gain-of-resistance" phenotype are largely unknown, a concerted research effort is needed to identify the underlying basis for the occurrence of this phenotype and, in parallel, to explore the possibility that the phenotype may be a product of wild-type p53 gain-of-function effects. Such studies are essential to lay the foundation for a rational therapeutic approach in the treatment of resistant wild-type p53 cancers. |
| | |
Authors:
|
Michelle Martinez-Rivera; Zahid H Siddik |
Related Documents
:
|
12213184 - Regular use of aspirin and pancreatic cancer risk. 12658384 - Gene expression screening using a cdna macroarray to clarify the mechanisms of peritone... 10872424 - Inheritance of pancreatic cancer in pancreatic cancer-prone families. 19718354 - Redefining resection margin status in pancreatic cancer. 22126844 - Higher complication risk of totally implantable venous access port systems in patients ... 20443694 - Update: turning the heat on cancer. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2011-12-26 |
Journal Detail:
|
Title: Biochemical pharmacology Volume: 83 ISSN: 1873-2968 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2012 Apr |
Date Detail:
|
Created Date: 2012-03-12 Completed Date: 2012-05-16 Revised Date: 2013-04-17 |
Medline Journal Info:
|
Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
|
Languages: eng Pagination: 1049-62 Citation Subset: IM |
Copyright Information:
|
Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, 77030, United States. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antineoplastic Agents
/
pharmacology Apoptosis / drug effects, genetics Cell Cycle Checkpoints / drug effects, genetics Drug Resistance, Neoplasm / genetics* Genes, p53* Humans Mutation Neoplasms / drug therapy*, genetics*, pathology Phosphorylation Protein Processing, Post-Translational Tumor Suppressor Protein p53 / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
CA127263/CA/NCI NIH HHS; CA160687/CA/NCI NIH HHS; CA16672/CA/NCI NIH HHS; R01 CA127263-05/CA/NCI NIH HHS; R01 CA160687/CA/NCI NIH HHS; R01 CA160687-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Acquired resistance to drugs targeting receptor tyrosine kinases.
Next Document: Mutant BRAF induces DNA strand breaks, activates DNA damage response pathway, and up-regulates gluco...