Revisiting p53 for cancer-specific chemo- and radiotherapy: ten years after. Cell Cycle 2014;13(5):710-3
Date
02/15/2014Pubmed ID
24526114Pubmed Central ID
PMC3979907DOI
10.4161/cc.28108Scopus ID
2-s2.0-84897969159 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
Despite intense studies, highly effective therapeutic strategies against cancer have not yet been fully exploited, because few true cancer-specific targets have been identified. Most modalities, perhaps with the exception of radiation therapy, target proliferating cells, which are also abundant in normal tissues. Thus, most current cancer treatments have significant side effects. More than 10 years ago, the tumor suppressor p53 was first explored as a cancer-specific target. At the time, the approach was to introduce a normal p53 gene into mutant p53 (mp53) tumor cells to induce cell cycle arrest and apoptosis. However, this strategy did not hold up and mostly failed in subsequent clinical studies. Recent research developments have now returned p53 to the limelight. Several studies have reported that mutant or null p53 tumor cells undergo apoptosis more easily than genetically matched, normal p53 counterparts when inhibiting a specific stress kinase in combination with standard chemotherapy or when exposed to an ataxia-telangiectasia mutated (ATM) kinase inhibitor and radiation, thus achieving true cancer specificity in animal tumor models. This short review highlights several of these recent studies, discusses possible mechanism(s) for mp53-mediated "synthetic lethality," and the implications for cancer therapy.
Author List
Beckta JM, Ahmad SF, Yang H, Valerie KAuthor
Hu Yang PhD Chair, Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Apoptosis
Ataxia Telangiectasia Mutated Proteins
Genetic Therapy
Humans
Mutation
Neoplasms
Protein Kinase Inhibitors
Tumor Suppressor Protein p53