Reference Detail

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	Vol	Issue	Date	Pages	Journal Short Title
Cancer treatment reviews	40	10	2014 Dec	1153-60	Cancer Treat Rev

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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Showing 1 to 363 of 363 entries

Molecular Profile	Treatment Approach
TP53 A129Tfs*12	p53 Gene Therapy
TP53 A138P	p53 Gene Therapy
TP53 A138P	p53 Activator
TP53 A138T	p53 Gene Therapy
TP53 A138T	p53 Activator
TP53 A138V	p53 Gene Therapy
TP53 A138V	p53 Activator
TP53 A159fs	p53 Gene Therapy
TP53 A159V	p53 Gene Therapy
TP53 A159V	p53 Activator
TP53 A307fs	p53 Gene Therapy
TP53 A347D	p53 Gene Therapy
TP53 A347D	p53 Activator
TP53 A88fs	p53 Gene Therapy
TP53 C124*	p53 Gene Therapy
TP53 C124fs	p53 Gene Therapy
TP53 C135Afs*35	p53 Gene Therapy
TP53 C135F	p53 Activator
TP53 C135F	p53 Gene Therapy
TP53 C135fs	p53 Gene Therapy
TP53 C135S	p53 Activator
TP53 C135S	p53 Gene Therapy
TP53 C141Afs*5	p53 Gene Therapy
TP53 C141Y	p53 Activator
TP53 C141Y	p53 Gene Therapy
TP53 C176*	p53 Gene Therapy
TP53 C176Afs*71	p53 Gene Therapy
TP53 C176F	p53 Activator
TP53 C176F	p53 Gene Therapy
TP53 C238S	p53 Activator
TP53 C238S	p53 Gene Therapy
TP53 C242Afs*5	p53 Gene Therapy
TP53 C242fs	p53 Gene Therapy
TP53 C242S	p53 Activator
TP53 C242S	p53 Gene Therapy
TP53 C242Y	p53 Activator
TP53 C242Y	p53 Gene Therapy
TP53 C275*	p53 Gene Therapy
TP53 C275Wfs*70	p53 Gene Therapy
TP53 C277F	p53 Activator
TP53 C277F	p53 Gene Therapy
TP53 D21fs	p53 Gene Therapy
TP53 D228fs	p53 Gene Therapy
TP53 D281E	p53 Activator
TP53 D281E	p53 Gene Therapy
TP53 D324Afs*32	p53 Gene Therapy
TP53 D7A	p53 Gene Therapy
TP53 D7A	p53 Activator
TP53 E180*	p53 Gene Therapy
TP53 E180K	p53 Activator
TP53 E180K	p53 Gene Therapy
TP53 E198*	p53 Gene Therapy
TP53 E198_G199del	p53 Gene Therapy
TP53 E198_G199del	p53 Activator
TP53 E204fs	p53 Gene Therapy
TP53 E224*	p53 Gene Therapy
TP53 E224fs	p53 Gene Therapy
TP53 E258*	p53 Gene Therapy
TP53 E258D	p53 Gene Therapy
TP53 E258D	p53 Activator
TP53 E271*	p53 Gene Therapy
TP53 E285V	p53 Gene Therapy
TP53 E285V	p53 Activator
TP53 E286K	p53 Gene Therapy
TP53 E286K	p53 Activator
TP53 E287A	p53 Gene Therapy
TP53 E287A	p53 Activator
TP53 E294*	p53 Activator
TP53 E294*	p53 Gene Therapy
TP53 E298*	p53 Gene Therapy
TP53 E326*	p53 Gene Therapy
TP53 E336*	p53 Gene Therapy
TP53 E349*	p53 Gene Therapy
TP53 F109Sfs*14	p53 Gene Therapy
TP53 F134L	p53 Activator
TP53 F134L	p53 Gene Therapy
TP53 F212fs	p53 Gene Therapy
TP53 G154fs	p53 Gene Therapy
TP53 G226Afs*21	p53 Activator
TP53 G226Afs*21	p53 Gene Therapy
TP53 G244fs	p53 Gene Therapy
TP53 G244S	p53 Activator
TP53 G244S	p53 Gene Therapy
TP53 G245A	p53 Gene Therapy
TP53 G245A	p53 Activator
TP53 G245C	p53 Gene Therapy
TP53 G245C	p53 Activator
TP53 G245D	p53 Gene Therapy
TP53 G245D	p53 Activator
TP53 G245fs	p53 Gene Therapy
TP53 G245R	p53 Gene Therapy
TP53 G245R	p53 Activator
TP53 G245S	p53 Gene Therapy
TP53 G245S	p53 Activator
TP53 G245V	p53 Gene Therapy
TP53 G245V	p53 Activator
TP53 G266R	p53 Gene Therapy
TP53 G266R	p53 Activator
TP53 H168P	p53 Activator
TP53 H168P	p53 Gene Therapy
TP53 H168R	p53 Gene Therapy
TP53 H168R	p53 Activator
TP53 H178Tfs*69	p53 Gene Therapy
TP53 H179L	p53 Gene Therapy
TP53 H179L	p53 Activator
TP53 H179N	p53 Gene Therapy
TP53 H179N	p53 Activator
TP53 H179Q	p53 Activator
TP53 H179Q	p53 Gene Therapy
TP53 H179Y	p53 Activator
TP53 H179Y	p53 Gene Therapy
TP53 H193P	p53 Gene Therapy
TP53 H193P	p53 Activator
TP53 H214Qfs*7	p53 Gene Therapy
TP53 H233_Y234del	p53 Activator
TP53 H233_Y234del	p53 Gene Therapy
TP53 I195*	p53 Gene Therapy
TP53 I251S	p53 Activator
TP53 I251S	p53 Gene Therapy
TP53 I254T	p53 Gene Therapy
TP53 I254T	p53 Activator
TP53 I255del	p53 Gene Therapy
TP53 I255del	p53 Activator
TP53 I332Pfs*14	p53 Gene Therapy
TP53 inact mut	p53 Gene Therapy
TP53 inact mut	p53 Activator
TP53 K132N	p53 Gene Therapy
TP53 K139fs	p53 Gene Therapy
TP53 K164*	p53 Gene Therapy
TP53 K351E	p53 Activator
TP53 K351E	p53 Gene Therapy
TP53 K351Q	p53 Activator
TP53 K351Q	p53 Gene Therapy
TP53 K357R	p53 Gene Therapy
TP53 K357R	p53 Activator
TP53 L111fs	p53 Gene Therapy
TP53 L111Wfs*12	p53 Activator
TP53 L111Wfs*12	p53 Gene Therapy
TP53 L114fs	p53 Gene Therapy
TP53 L194F	p53 Activator
TP53 L194F	p53 Gene Therapy
TP53 L194R	p53 Activator
TP53 L194R	p53 Gene Therapy
TP53 L201Ffs*8	p53 Activator
TP53 L201Ffs*8	p53 Gene Therapy
TP53 L257Gfs*6	p53 Gene Therapy
TP53 L348A	p53 Gene Therapy
TP53 L348A	p53 Activator
TP53 L348S	p53 Gene Therapy
TP53 L348S	p53 Activator
TP53 M246I	p53 Activator
TP53 M246I	p53 Gene Therapy
TP53 M246R	p53 Gene Therapy
TP53 M246R	p53 Activator
TP53 M40fs	p53 Gene Therapy
TP53 M44fs	p53 Gene Therapy
TP53 N131fs	p53 Gene Therapy
TP53 N235D	p53 Gene Therapy
TP53 N235D	p53 Activator
TP53 N239S	p53 Gene Therapy
TP53 N239S	p53 Activator
TP53 N30fs	p53 Gene Therapy
TP53 N345*	p53 Gene Therapy
TP53 N345Ifs*26	p53 Gene Therapy
TP53 P128fs	p53 Gene Therapy
TP53 P151H	p53 Gene Therapy
TP53 P151H	p53 Activator
TP53 P151S	p53 Gene Therapy
TP53 P151S	p53 Activator
TP53 P152fs	p53 Gene Therapy
TP53 P152L	p53 Gene Therapy
TP53 P152L	p53 Activator
TP53 P190S	p53 Activator
TP53 P190S	p53 Gene Therapy
TP53 P191fs	p53 Gene Therapy
TP53 P219fs	p53 Activator
TP53 P219fs	p53 Gene Therapy
TP53 P219S	p53 Gene Therapy
TP53 P219S	p53 Activator
TP53 P278A	p53 Gene Therapy
TP53 P278A	p53 Activator
TP53 P278S	p53 Activator
TP53 P278S	p53 Gene Therapy
TP53 P27Lfs*17	p53 Gene Therapy
TP53 P301fs	p53 Gene Therapy
TP53 P72fs	p53 Gene Therapy
TP53 P82Gfs*66	p53 Gene Therapy
TP53 P82Rfs*41	p53 Gene Therapy
TP53 P98A	p53 Gene Therapy
TP53 P98A	p53 Activator
TP53 P98fs	p53 Gene Therapy
TP53 Q104*	p53 Gene Therapy
TP53 Q136*	p53 Gene Therapy
TP53 Q144*	p53 Gene Therapy
TP53 Q165*	p53 Gene Therapy
TP53 Q192*	p53 Gene Therapy
TP53 Q317*	p53 Gene Therapy
TP53 Q331*	p53 Gene Therapy
TP53 R110L	p53 Gene Therapy
TP53 R110L	p53 Activator
TP53 R110P	p53 Gene Therapy
TP53 R110P	p53 Activator
TP53 R110Vfs*13	p53 Gene Therapy
TP53 R156P	p53 Gene Therapy
TP53 R156P	p53 Activator
TP53 R158fs	p53 Gene Therapy
TP53 R158H	p53 Activator
TP53 R158H	p53 Gene Therapy
TP53 R158L	p53 Activator
TP53 R158L	p53 Gene Therapy
TP53 R175A	p53 Activator
TP53 R175A	p53 Gene Therapy
TP53 R175H	p53 Gene Therapy
TP53 R175H	p53 Activator
TP53 R175L	p53 Gene Therapy
TP53 R175L	p53 Activator
TP53 R181P	p53 Activator
TP53 R181P	p53 Gene Therapy
TP53 R196*	p53 Gene Therapy
TP53 R196G	p53 Activator
TP53 R196G	p53 Gene Therapy
TP53 R209fs	p53 Gene Therapy
TP53 R209Kfs*6	p53 Gene Therapy
TP53 R213*	p53 Gene Therapy
TP53 R213fs	p53 Gene Therapy
TP53 R248E	p53 Gene Therapy
TP53 R248E	p53 Activator
TP53 R248G	p53 Gene Therapy
TP53 R248G	p53 Activator
TP53 R248L	p53 Activator
TP53 R248L	p53 Gene Therapy
TP53 R248P	p53 Activator
TP53 R248P	p53 Gene Therapy
TP53 R248Q	p53 Gene Therapy
TP53 R248Q	p53 Activator
TP53 R248W	p53 Activator
TP53 R248W	p53 Gene Therapy
TP53 R249G	p53 Activator
TP53 R249G	p53 Gene Therapy
TP53 R249K	p53 Activator
TP53 R249K	p53 Gene Therapy
TP53 R249M	p53 Gene Therapy
TP53 R249M	p53 Activator
TP53 R249S	p53 Activator
TP53 R249S	p53 Gene Therapy
TP53 R249T	p53 Activator
TP53 R249T	p53 Gene Therapy
TP53 R249W	p53 Gene Therapy
TP53 R249W	p53 Activator
TP53 R267W	p53 Gene Therapy
TP53 R267W	p53 Activator
TP53 R273*	p53 Gene Therapy
TP53 R273C	p53 Activator
TP53 R273C	p53 Gene Therapy
TP53 R273H	p53 Gene Therapy
TP53 R273H	p53 Activator
TP53 R273L	p53 Activator
TP53 R273L	p53 Gene Therapy
TP53 R273P	p53 Activator
TP53 R273P	p53 Gene Therapy
TP53 R273S	p53 Gene Therapy
TP53 R273S	p53 Activator
TP53 R273W	p53 Activator
TP53 R273W	p53 Gene Therapy
TP53 R280A	p53 Activator
TP53 R280A	p53 Gene Therapy
TP53 R280D	p53 Gene Therapy
TP53 R280D	p53 Activator
TP53 R280I	p53 Activator
TP53 R280I	p53 Gene Therapy
TP53 R280T	p53 Activator
TP53 R280T	p53 Gene Therapy
TP53 R282D	p53 Activator
TP53 R282D	p53 Gene Therapy
TP53 R282fs	p53 Gene Therapy
TP53 R282Q	p53 Activator
TP53 R282Q	p53 Gene Therapy
TP53 R282W	p53 Gene Therapy
TP53 R282W	p53 Activator
TP53 R283del	p53 Gene Therapy
TP53 R283del	p53 Activator
TP53 R306*	p53 Gene Therapy
TP53 R333fs	p53 Gene Therapy
TP53 R333Vfs*12	p53 Gene Therapy
TP53 R335fs	p53 Gene Therapy
TP53 R335H	p53 Gene Therapy
TP53 R335H	p53 Activator
TP53 R337C	p53 Activator
TP53 R337C	p53 Gene Therapy
TP53 R337L	p53 Gene Therapy
TP53 R337L	p53 Activator
TP53 R337P	p53 Gene Therapy
TP53 R337P	p53 Activator
TP53 R342*	p53 Gene Therapy
TP53 R342fs	p53 Gene Therapy
TP53 R65*	p53 Gene Therapy
TP53 S166Cfs*6	p53 Gene Therapy
TP53 S166Yfs*4	p53 Gene Therapy
TP53 S20fs	p53 Gene Therapy
TP53 S215fs	p53 Gene Therapy
TP53 S215G	p53 Gene Therapy
TP53 S215G	p53 Activator
TP53 S215I	p53 Activator
TP53 S215I	p53 Gene Therapy
TP53 S227fs	p53 Gene Therapy
TP53 S227Lfs*20	p53 Gene Therapy
TP53 S240I	p53 Gene Therapy
TP53 S240I	p53 Activator
TP53 S240Kfs*25	p53 Gene Therapy
TP53 S241F	p53 Gene Therapy
TP53 S241F	p53 Activator
TP53 S241fs	p53 Gene Therapy
TP53 S241Y	p53 Activator
TP53 S241Y	p53 Gene Therapy
TP53 S46fs	p53 Gene Therapy
TP53 S90fs	p53 Gene Therapy
TP53 T118fs	p53 Gene Therapy
TP53 T118Qfs*5	p53 Gene Therapy
TP53 T150fs	p53 Gene Therapy
TP53 T155fs	p53 Gene Therapy
TP53 T211Ffs*4	p53 Gene Therapy
TP53 T256fs	p53 Gene Therapy
TP53 T329fs	p53 Gene Therapy
TP53 V122fs	p53 Gene Therapy
TP53 V143A	p53 Gene Therapy
TP53 V143A	p53 Activator
TP53 V157fs	p53 Gene Therapy
TP53 V173A	p53 Gene Therapy
TP53 V173A	p53 Activator
TP53 V173M	p53 Gene Therapy
TP53 V173M	p53 Activator
TP53 V272M	p53 Activator
TP53 V272M	p53 Gene Therapy
TP53 V274F	p53 Gene Therapy
TP53 V274F	p53 Activator
TP53 V274fs	p53 Gene Therapy
TP53 W146*	p53 Gene Therapy
TP53 W53*	p53 Gene Therapy
TP53 W91fs	p53 Gene Therapy
TP53 W91Gfs*32	p53 Gene Therapy
TP53 Y103*	p53 Gene Therapy
TP53 Y103fs	p53 Gene Therapy
TP53 Y103Sfs*18	p53 Gene Therapy
TP53 Y126C	p53 Activator
TP53 Y126C	p53 Gene Therapy
TP53 Y126H	p53 Activator
TP53 Y126H	p53 Gene Therapy
TP53 Y163*	p53 Gene Therapy
TP53 Y163C	p53 Gene Therapy
TP53 Y163C	p53 Activator
TP53 Y205*	p53 Gene Therapy
TP53 Y205C	p53 Gene Therapy
TP53 Y205C	p53 Activator
TP53 Y220C	p53 Activator
TP53 Y220C	p53 Gene Therapy
TP53 Y234C	p53 Activator
TP53 Y234C	p53 Gene Therapy
TP53 Y234H	p53 Gene Therapy
TP53 Y234H	p53 Activator
TP53 Y236C	p53 Activator
TP53 Y236C	p53 Gene Therapy
TP53 Y327L	p53 Activator
TP53 Y327L	p53 Gene Therapy

Showing 1 to 363 of 363 entries

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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
No data available in table

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
No data available in table

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
No data available in table

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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
No data available in table

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