Drug discovery and the p53 family.
The tumour suppressor activity of p53 plays a major role in limiting abnormal proliferation, and inactivation of the p53 response is becoming increasingly accepted as a hallmark of cancer. In contrast, both p63 and p73, which are close relatives of p53, are rarely mutated in tumour cells. At a theoretical level, therapeutic approaches that reinstate p53 activity, or augment p63 and p73, provide plausible and potentially efficacious routes towards new cancer treatments. Equally important is the clinical need to increase the efficacy of conventional anti-cancer drugs. Incapacitating the p53 response to limit the side effects in healthy cells may be one approach towards increasing the therapeutic window of many current anti-cancer drugs. Nevertheless, while cancer drug discovery focussed on p53 is an exciting and realistic possibility, translating this concept into a clinical setting is likely to be challenging.
Demonacos
Constantinos
C
Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, U.K.
La Thangue
Nicholas B
NB
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000819:agonists / Q000378:metabolism; D015195:Drug Design; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000819:agonists / Q000378:metabolism; D010750:Phosphoproteins / Q000819:agonists / Q000378:metabolism; D015534:Trans-Activators / Q000819:agonists / Q000378:metabolism; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins