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Ref Type Journal Article
PMID (25455730)
Authors Duffy MJ, Synnott NC, McGowan PM, Crown J, O'Connor D, Gallagher WM
Title p53 as a target for the treatment of cancer.
Journal Cancer treatment reviews
Vol 40
Issue 10
Date 2014 Dec
URL
Abstract Text TP53 (p53) is the most frequently mutated gene in cancer, being altered in approximately 50% of human malignancies. In most, if not all, cancers lacking mutation, wild-type (WT) p53 is inactivated by interaction with cellular (MDM2/MDM4) or viral proteins, leading to its degradation. Because of its near universal alteration in cancer, p53 is an attractive target for the development of new targeted therapies for this disease. However, until recently, p53 was widely regarded as ‘‘undruggable’’. This situation has now changed, as several compounds have become available that can restore wild-type properties to mutant p53 (e.g., PRIMA-1 and PRIMA-1MET). Other compounds are available that prevent the binding of MDM2/MDM4 to WT p53, thereby blocking its degradation (e.g., nutlins). Anti-mutant p53 compounds are potentially most useful in cancers with a high prevalence of p53 mutations. These include difficult-totreat tumors such as high grade serous ovarian cancer, triple-negative breast cancer and squamous lung cancer. MDM2/4 antagonists, on the other hand, are likely to be efficacious in malignancies in which MDM2 or MDM4 is overexpressed such as sarcomas, neuroblastomas and specific childhood leukemias. Presently, early clinical trials are ongoing evaluating the anti-mutant p53 agent, PRIMA-1MET, and specific MDM2–p53 nutlin antagonists.

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Molecular Profile Treatment Approach
TP53 R110L p53 Gene Therapy
TP53 V143A p53 Activator
TP53 Q192* p53 Gene Therapy
TP53 E204fs p53 Gene Therapy
TP53 R175H p53 Gene Therapy
TP53 Y126C p53 Activator
TP53 R273S p53 Activator
TP53 S227Lfs*20 p53 Gene Therapy
TP53 C135Afs*35 p53 Gene Therapy
TP53 E294* p53 Activator
TP53 W91Gfs*32 p53 Gene Therapy
TP53 G245V p53 Gene Therapy
TP53 P152L p53 Activator
TP53 H179N p53 Gene Therapy
TP53 V274fs p53 Gene Therapy
TP53 R65* p53 Gene Therapy
TP53 L194R p53 Gene Therapy
TP53 M246R p53 Activator
TP53 F134L p53 Gene Therapy
TP53 D7A p53 Gene Therapy
TP53 M246I p53 Activator
TP53 R248G p53 Gene Therapy
TP53 G266R p53 Gene Therapy
TP53 S241F p53 Gene Therapy
TP53 C242Y p53 Gene Therapy
TP53 P98fs p53 Gene Therapy
TP53 G154fs p53 Gene Therapy
TP53 P190S p53 Gene Therapy
TP53 P278A p53 Gene Therapy
TP53 R333fs p53 Gene Therapy
TP53 Y126C p53 Gene Therapy
TP53 S20fs p53 Gene Therapy
TP53 F134L p53 Activator
TP53 R337C p53 Activator
TP53 H178Tfs*69 p53 Gene Therapy
TP53 G245C p53 Activator
TP53 N345Ifs*26 p53 Gene Therapy
TP53 A307fs p53 Gene Therapy
TP53 G244S p53 Gene Therapy
TP53 G245R p53 Activator
TP53 H214Qfs*7 p53 Gene Therapy
TP53 T211Ffs*4 p53 Gene Therapy
TP53 C242fs p53 Gene Therapy
TP53 R249S p53 Activator
TP53 Y234C p53 Gene Therapy
TP53 V272M p53 Gene Therapy
TP53 R249T p53 Activator
TP53 G226Afs*21 p53 Activator
TP53 E180K p53 Activator
TP53 R248P p53 Gene Therapy
TP53 Q136* p53 Gene Therapy
TP53 R249S p53 Gene Therapy
TP53 E286K p53 Gene Therapy
TP53 R249W p53 Gene Therapy
TP53 V122fs p53 Gene Therapy
TP53 G245D p53 Gene Therapy
TP53 Q317* p53 Gene Therapy
TP53 W53* p53 Gene Therapy
TP53 R282D p53 Gene Therapy
TP53 A347D p53 Activator
TP53 R337L p53 Gene Therapy
TP53 R181P p53 Activator
TP53 E286K p53 Activator
TP53 R248Q p53 Gene Therapy
TP53 R282Q p53 Gene Therapy
TP53 R209Kfs*6 p53 Gene Therapy
TP53 R158fs p53 Gene Therapy
TP53 R273C p53 Gene Therapy
TP53 K357R p53 Gene Therapy
TP53 R248L p53 Gene Therapy
TP53 V173A p53 Gene Therapy
TP53 R282Q p53 Activator
TP53 Y234C p53 Activator
TP53 S215G p53 Gene Therapy
TP53 Y205* p53 Gene Therapy
TP53 R248Q p53 Activator
TP53 Y163* p53 Gene Therapy
TP53 P27Lfs*17 p53 Gene Therapy
TP53 R282W p53 Activator
TP53 I255del p53 Gene Therapy
TP53 L348S p53 Gene Therapy
TP53 R273H p53 Activator
TP53 R248P p53 Activator
TP53 P82Gfs*66 p53 Gene Therapy
TP53 R337P p53 Activator
TP53 P128fs p53 Gene Therapy
TP53 V173M p53 Activator
TP53 E180* p53 Gene Therapy
TP53 R213fs p53 Gene Therapy
TP53 C275Wfs*70 p53 Gene Therapy
TP53 M44fs p53 Gene Therapy
TP53 C176F p53 Activator
TP53 L114fs p53 Gene Therapy
TP53 C176Afs*71 p53 Gene Therapy
TP53 R249K p53 Gene Therapy
TP53 T118Qfs*5 p53 Gene Therapy
TP53 H179N p53 Activator
TP53 H168R p53 Gene Therapy
TP53 C141Afs*5 p53 Gene Therapy
TP53 R342fs p53 Gene Therapy
TP53 R337P p53 Gene Therapy
TP53 M40fs p53 Gene Therapy
TP53 C135F p53 Activator
TP53 R280D p53 Activator
TP53 P219fs p53 Gene Therapy
TP53 P152L p53 Gene Therapy
TP53 R273C p53 Activator
TP53 S240Kfs*25 p53 Gene Therapy
TP53 R175A p53 Activator
TP53 H179Q p53 Gene Therapy
TP53 Y327L p53 Gene Therapy
TP53 H179L p53 Activator
TP53 Y163C p53 Activator
TP53 Q331* p53 Gene Therapy
TP53 Y236C p53 Activator
TP53 E349* p53 Gene Therapy
TP53 R273P p53 Gene Therapy
TP53 D228fs p53 Gene Therapy
TP53 Q165* p53 Gene Therapy
TP53 R196G p53 Gene Therapy
TP53 A347D p53 Gene Therapy
TP53 Y163C p53 Gene Therapy
TP53 W146* p53 Gene Therapy
TP53 R249G p53 Gene Therapy
TP53 C141Y p53 Gene Therapy
TP53 N345* p53 Gene Therapy
TP53 P219fs p53 Activator
TP53 A159V p53 Activator
TP53 T118fs p53 Gene Therapy
TP53 C124fs p53 Gene Therapy
TP53 R158L p53 Gene Therapy
TP53 C242S p53 Gene Therapy
TP53 K357R p53 Activator
TP53 L111fs p53 Gene Therapy
TP53 Y103* p53 Gene Therapy
TP53 R249K p53 Activator
TP53 M246R p53 Gene Therapy
TP53 inact mut p53 Activator
TP53 I195* p53 Gene Therapy
TP53 I254T p53 Gene Therapy
TP53 R280A p53 Activator
TP53 H179Y p53 Activator
TP53 R156P p53 Gene Therapy
TP53 R282W p53 Gene Therapy
TP53 F212fs p53 Gene Therapy
TP53 Q144* p53 Gene Therapy
TP53 R181P p53 Gene Therapy
TP53 G245S p53 Activator
TP53 E258D p53 Activator
TP53 R273L p53 Activator
TP53 G245V p53 Activator
TP53 G245S p53 Gene Therapy
TP53 G245A p53 Gene Therapy
TP53 P278S p53 Gene Therapy
TP53 R342* p53 Gene Therapy
TP53 F109Sfs*14 p53 Gene Therapy
TP53 E258D p53 Gene Therapy
TP53 R280D p53 Gene Therapy
TP53 R213* p53 Gene Therapy
TP53 R175H p53 Activator
TP53 Y103Sfs*18 p53 Gene Therapy
TP53 Y234H p53 Activator
TP53 C176F p53 Gene Therapy
TP53 E285V p53 Gene Therapy
TP53 E180K p53 Gene Therapy
TP53 N235D p53 Gene Therapy
TP53 G245A p53 Activator
TP53 R335H p53 Gene Therapy
TP53 A138T p53 Gene Therapy
TP53 C275* p53 Gene Therapy
TP53 R280A p53 Gene Therapy
TP53 P151S p53 Activator
TP53 R248W p53 Activator
TP53 C242Y p53 Activator
TP53 R248E p53 Activator
TP53 Y220C p53 Activator
TP53 R306* p53 Gene Therapy
TP53 N30fs p53 Gene Therapy
TP53 S241Y p53 Gene Therapy
TP53 C135F p53 Gene Therapy
TP53 C124* p53 Gene Therapy
TP53 H168R p53 Activator
TP53 V272M p53 Activator
TP53 R249W p53 Activator
TP53 P98A p53 Activator
TP53 E326* p53 Gene Therapy
TP53 P219S p53 Activator
TP53 Y236C p53 Gene Therapy
TP53 V173M p53 Gene Therapy
TP53 R196* p53 Gene Therapy
TP53 N239S p53 Gene Therapy
TP53 C135fs p53 Gene Therapy
TP53 R209fs p53 Gene Therapy
TP53 L257Gfs*6 p53 Gene Therapy
TP53 R273H p53 Gene Therapy
TP53 V274F p53 Gene Therapy
TP53 P278S p53 Activator
TP53 L194R p53 Activator
TP53 R110P p53 Gene Therapy
TP53 P82Rfs*41 p53 Gene Therapy
TP53 R280T p53 Gene Therapy
TP53 D281E p53 Activator
TP53 A159V p53 Gene Therapy
TP53 Y205C p53 Activator
TP53 E298* p53 Gene Therapy
TP53 V143A p53 Gene Therapy
TP53 P190S p53 Activator
TP53 P301fs p53 Gene Therapy
TP53 K351E p53 Gene Therapy
TP53 L111Wfs*12 p53 Gene Therapy
TP53 W91fs p53 Gene Therapy
TP53 R156P p53 Activator
TP53 R158H p53 Gene Therapy
TP53 R249M p53 Activator
TP53 Y220C p53 Gene Therapy
TP53 E287A p53 Activator
TP53 R335H p53 Activator
TP53 G226Afs*21 p53 Gene Therapy
TP53 Y205C p53 Gene Therapy
TP53 S215G p53 Activator
TP53 D7A p53 Activator
TP53 R249G p53 Activator
TP53 Y327L p53 Activator
TP53 K139fs p53 Gene Therapy
TP53 R158H p53 Activator
TP53 L348S p53 Activator
TP53 V157fs p53 Gene Therapy
TP53 R110P p53 Activator
TP53 E294* p53 Gene Therapy
TP53 A159fs p53 Gene Therapy
TP53 S215I p53 Activator
TP53 E336* p53 Gene Therapy
TP53 S241F p53 Activator
TP53 E258* p53 Gene Therapy
TP53 R267W p53 Activator
TP53 L194F p53 Activator
TP53 C277F p53 Gene Therapy
TP53 R110L p53 Activator
TP53 R158L p53 Activator
TP53 I251S p53 Activator
TP53 R175L p53 Gene Therapy
TP53 G245C p53 Gene Therapy
TP53 R175A p53 Gene Therapy
TP53 L111Wfs*12 p53 Activator
TP53 R110Vfs*13 p53 Gene Therapy
TP53 N235D p53 Activator
TP53 E198* p53 Gene Therapy
TP53 R248W p53 Gene Therapy
TP53 S215I p53 Gene Therapy
TP53 R175L p53 Activator
TP53 R248L p53 Activator
TP53 R333Vfs*12 p53 Gene Therapy
TP53 C238S p53 Gene Therapy
TP53 P278A p53 Activator
TP53 V274F p53 Activator
TP53 H193P p53 Activator
TP53 S227fs p53 Gene Therapy
TP53 H193P p53 Gene Therapy
TP53 R280I p53 Activator
TP53 S46fs p53 Gene Therapy
TP53 R249T p53 Gene Therapy
TP53 P72fs p53 Gene Therapy
TP53 R282fs p53 Gene Therapy
TP53 L194F p53 Gene Therapy
TP53 C242Afs*5 p53 Gene Therapy
TP53 Y234H p53 Gene Therapy
TP53 N239S p53 Activator
TP53 R273* p53 Gene Therapy
TP53 A138T p53 Activator
TP53 C242S p53 Activator
TP53 K351Q p53 Gene Therapy
TP53 R273W p53 Gene Therapy
TP53 I332Pfs*14 p53 Gene Therapy
TP53 R282D p53 Activator
TP53 L348A p53 Activator
TP53 N131fs p53 Gene Therapy
TP53 G244fs p53 Gene Therapy
TP53 G245R p53 Gene Therapy
TP53 R249M p53 Gene Therapy
TP53 C277F p53 Activator
TP53 Y103fs p53 Gene Therapy
TP53 M246I p53 Gene Therapy
TP53 H179Y p53 Gene Therapy
TP53 R280T p53 Activator
TP53 S240I p53 Gene Therapy
TP53 T329fs p53 Gene Therapy
TP53 G245D p53 Activator
TP53 P151H p53 Gene Therapy
TP53 R335fs p53 Gene Therapy
TP53 G244S p53 Activator
TP53 I251S p53 Gene Therapy
TP53 C238S p53 Activator
TP53 R267W p53 Gene Therapy
TP53 P219S p53 Gene Therapy
TP53 K351Q p53 Activator
TP53 P151S p53 Gene Therapy
TP53 R337C p53 Gene Therapy
TP53 R273W p53 Activator
TP53 C135S p53 Activator
TP53 R283del p53 Activator
TP53 E287A p53 Gene Therapy
TP53 R248E p53 Gene Therapy
TP53 P98A p53 Gene Therapy
TP53 C141Y p53 Activator
TP53 E224* p53 Gene Therapy
TP53 K351E p53 Activator
TP53 R337L p53 Activator
TP53 L348A p53 Gene Therapy
TP53 R283del p53 Gene Therapy
TP53 C176* p53 Gene Therapy
TP53 K132N p53 Gene Therapy
TP53 R273L p53 Gene Therapy
TP53 P152fs p53 Gene Therapy
TP53 H179Q p53 Activator
TP53 S241Y p53 Activator
TP53 S240I p53 Activator
TP53 S90fs p53 Gene Therapy
TP53 P191fs p53 Gene Therapy
TP53 H179L p53 Gene Therapy
TP53 D281E p53 Gene Therapy
TP53 P151H p53 Activator
TP53 I254T p53 Activator
TP53 R248G p53 Activator
TP53 R273S p53 Gene Therapy
TP53 R196G p53 Activator
TP53 G266R p53 Activator
TP53 inact mut p53 Gene Therapy
TP53 R273P p53 Activator
TP53 S215fs p53 Gene Therapy
TP53 I255del p53 Activator
TP53 E224fs p53 Gene Therapy
TP53 R280I p53 Gene Therapy
TP53 V173A p53 Activator
TP53 C135S p53 Gene Therapy
TP53 E285V p53 Activator
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References