p53-Based cyclotherapy: exploiting the 'guardian of the genome' to protect normal cells from cytotoxic therapy

• Published in: British journal of cancer Vol. 109; no. 12; pp. 2954 - 2958
• Main Authors: RAO, B, LAIN, S, THOMPSON, A. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 10.12.2013
• Subjects: Animals; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Biological and medical sciences; Bone marrow; Breast Neoplasms - drug therapy; Cancer och onkologi; Cancer therapies; Cell cycle; Cell division; Cell Growth Processes - genetics; Cell Growth Processes - physiology; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Dactinomycin - pharmacology; Dactinomycin - therapeutic use; DNA damage; Drug dosages; Farmakologi och toxikologi; Female; Genes; Genome - drug effects; Genomes; Humans; Imidazoles - pharmacology; Imidazoles - therapeutic use; Kinases; Klinisk medicin; Medical sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mini Review; Phosphorylation; Piperazines - pharmacology; Piperazines - therapeutic use; Proteins; Toxicity; Tumor Suppressor Protein p53 - metabolism; Tumors; Actinomycin; actinomycin D; Cell therapy; Nutlin; nutlin-3; Cytotoxicity; p53; Chemotherapy; Treatment; Cancerology; TP53 Gene; cyclotherapy; Genome; Protection; chemoprotection; Tumor suppressor gene
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2013.702

Side effects of chemotherapy are a major impediment in the treatment of cancer. Cyclotherapy is an emerging therapeutic strategy for protecting normal cells from the side effects of chemotherapy. Low, non-genotoxic doses of known p53 activators can be used to induce p53-dependent cell cycle arrest in normal cells bearing wild-type p53. This cytostatic effect of p53 can protect normal cells from the toxicity of S- or M-phase poisons. Here, we have reviewed existing cyclotherapy regimens using two well-known p53 activators, nutlin-3 and actinomycin D. We have highlighted an exemplar clinical perspective for cyclotherapy in breast cancer. The recent development of novel stapled peptides as activators of p53 without the corresponding cytotoxicity holds great promise for cyclotherapy to enhance the therapeutic window of existing chemotherapy drugs.