Cancer Family
Neoplasm
CI-CAN-00000001Explore in graph →
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Cancer Family
CI-CAN-00000001Explore in graph →
Variants & evidence
8,147 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| TP53 Mutation6 | ||||||||
| Tamoxifen | Malignant Breast Neoplasm | Predictive | C | Supports Resistance | 1 | accepted | EID2784In a study 202 breast cancer patients undergoing tamoxifen treatment, a higher frequency of wildtype TP53 patients responded to treatment compared to those with mutations in TP53 (66% wild-type vs. 31… (full text at CIViC) PMID 10786679 · Berns et al., 2000 · Open in CIViC | civic |
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID7978In a trial of 68 glioblastoma patients treated with either temozolomide or semustine, 24 patients were found to have TP53 mutations at codons 175, 248, or 273. Kaplan-Meier analysis of the 35 patients… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| VEGF/VEGFR Inhibitors | Malignant NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID11709In this trial involving 500 patients, 188 individuals received treatment with VEGF/VEGFR inhibitors. Among them, 106 patients had tumors containing TP53 mutations. The analysis revealed a higher rate … (full text at CIViC) PMID 27466356 · Wheler et al., 2016 · Open in CIViC | civic |
| Venetoclax | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Does Not Support Resistance | 2 | submitted | EID6074In patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, patients with deletion 17p and/or mutations in TP53 (N=24) were not more likely to have progressive dis… (full text at CIViC) PMID 28473407 · Anderson et al., 2017 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaALIAS | Predictive | B | Does Not Support Resistance | 2 | rejected | EID12076In patients with relapsed /refractory chronic lymphocytes leukemia or small lymphocytic lymphoma, patients with deletion 17p and/or mutations in TP53 (N=24) were not more likely to have progressive di… (full text at CIViC) PMID 28473407 · Anderson et al., 2017 · Open in CIViC | civic |
| Vismodegib | Medulloblastoma, SHH-Activated, TP53-MutantALIAS | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID8348Two phase II studies (PBTC-025B, n=31, age ≥ 22 years; PBTC-032, n=12, age 3-21 years) assessed the targeted efficacy of vismodegib, an SMO inhibitor, in patients with recurrent sonic hedgehog subgrou… (full text at CIViC) PMID 26169613 · Robinson et al., 2015 · Open in CIViC | civic |
| Deletion + TP53 Mutation1 | ||||||||
| (prognostic) | Kidney Wilms TumorALIAS | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID1283540 diffuse anaplasia in Wilms tumours (DAWT) samples were tested using copy number (n = 32) and gene expression (n = 36) arrays. 22 had TP53 mutations and 20 of these also had 17p loss. An increased r… (full text at CIViC) PMID 25313908 · Maschietto et al., 2014 · Open in CIViC | civic |
| TP53 Overexpression4 | ||||||||
| (prognostic) | Malignant Ovarian Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID2697p53 overexpression (>10% positive stained nuclei) was found in 110 cases from a 178 patient cohort with invasive ovarian carcinoma who had undergone surgery. Overexpression of p53 was correlated with … (full text at CIViC) PMID 11595686 · Reles et al., 2001 · Open in CIViC | civic |
| 〃 | Kidney Wilms TumorALIAS | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID894544 archival FFPE samples from confirmed cases of Wilms tumor with mean age 3 years 2 months, and taken from the most histologically aggressive parts of each tumor, were stained with p53 monoclonal ant… (full text at CIViC) PMID 21525573 · Jadali et al., 2011 · Open in CIViC | civic |
| Carboplatin + CisplatinSubstitutes | Malignant Ovarian Neoplasm | Predictive | ||||||
| TP53 P278S1 | ||||||||
| Vemurafenib | Skin Squamous Cell Carcinoma | Predictive | C | Supports Resistance | — | submitted | EID4419In a retrospective study of 23 patients with BRAF V600 mutation (a known vemurafenib sensitizing mutation) that developed cutaneous squamous-cell carcinoma upon treatment with vemurafenib monotherapy,… (full text at CIViC) PMID 22256804 · Su et al., 2012 · Open in CIViC | civic |
| TP53 P47S1 | ||||||||
| Cisplatin | Malignant NeoplasmALIAS | Predictive | E | Supports Resistance | 2 | accepted | EID1209The P47S (rs1800371) variant of TP53 is observed in 1.5% in African Americans and between 6% and 8% in certain African populations but has not been detected in Caucasian Americans. This paper reports … (full text at CIViC) PMID 27034505 · Jennis et al., 2016 · Open in CIViC | civic |
| TP53 P72R3 | ||||||||
| (prognostic) | Lung Carcinoma | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID1303Pooled data from 13 studies of patients with lung cancer found little effect of codon 72 allele on the overall survival of patients with lung cancer. Proline homozygous patients were correlated with s… (full text at CIViC) PMID 12840112 · Matakidou et al., 2003 · Open in CIViC | civic |
| 〃 | Malignant Cervical Neoplasm | Prognostic | B | Does Not Support Poor Outcome | 2 | accepted | EID1304In a relatively small meta-analysis of 119 women with cervical cancer and 127 controls, associations with homozygosity for arginine, and heterozygosity at this locus were both associated with odds rat… (full text at CIViC) PMID 11535556 · Klug et al., 2001 · Open in CIViC | civic |
| 〃 | OligodendrogliomaCURATED_BROADER | Prognostic | B | Does Not Support | ||||
| TP53 R158H1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID4886Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 R158L1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID4891Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 R175H7 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID389Breast cancer patients who harbor R175H mutation have worse overall survival than those with wild type TP53, but have better prognosis than those with R248W mutation. PMID 16489069 · Olivier et al., 2006 · Open in CIViC | civic |
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID7119Human mutant R175H p53 was stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression, resulting in viable cells. In contrast, p… (full text at CIViC) PMID 8099841 · Dittmer et al., 1993 · Open in CIViC | civic |
| 〃 | Malignant Endometrial NeoplasmCURATED_BROADER | Oncogenic | D | Supports | ||||
| TP53 H193R + TP53 R175H1 | ||||||||
| Pazopanib + VorinostatCombination | Sarcoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID7540In the phase I study of pazopanib and vorinostat in 36 patients with advanced solid tumors, detection of hotspot TP53 mutation was associated with a higher rate of SD ≥6 months/PR, longer median PFS (… (full text at CIViC) PMID 25669829 · Fu et al., 2015 · Open in CIViC | civic |
| TP53 R213*1 | ||||||||
| (predisposing) | Salivary Gland Mucinous Adenocarcinoma | Predisposing | E | Supports Pathogenic | 3 | submitted | EID7321As seen in Figure 1, the R213* mutation is predominantly found in colorectal and breast cancers. The variant was described as being a frequent p53 nonsense mutation in melanoma, kidney chromophobe, es… (full text at CIViC) PMID 28249646 · Panaccione et al., 2017 · Open in CIViC | civic |
| TP53 R213P1 | ||||||||
| EAP Protocol | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | — | accepted | EID2819In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| TP53 R248Q6 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID390Breast cancer patients who harbor a R248Q mutation (N=18) have worse overall survival than those with wild type TP53 (N=1460), but have better prognosis than those with a R248W mutation (N=8). PMID 16489069 · Olivier et al., 2006 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID391In breast cancer patients harboring TP53 mutation, mutations in DNA contact regions such as R248 (N=10, 6 at R248) are prognostic for a worse relapse-free survival compared to other non-silent mutatio… (full text at CIViC) PMID 9569050 · Berns et al., 1998 · Open in CIViC | civic |
| (predisposing) | Lymphoma | Predisposing | D | Supports Predisposition | 4 | accepted | ||
| TP53 R248W3 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID392In breast cancer patients harboring R248W mutation, the prognosis is worse than any other hotspot TP53 mutation, as well as worse than patients with wild type TP53. PMID 16489069 · Olivier et al., 2006 · Open in CIViC | civic |
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID7120Human mutant R248W p53 was stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression, resulting in viable cells. In contrast, p… (full text at CIViC) PMID 8099841 · Dittmer et al., 1993 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports | ||||
| TP53 R2491 | ||||||||
| Doxorubicin | Malignant Breast Neoplasm | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID399Breast tumors with R175H or R249 mutations are more responsive to doxorubicin than breast tumors with wild type TP53. PMID 9569050 · Berns et al., 1998 · Open in CIViC | civic |
| TP53 R249S1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4888Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 R273C4 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID395Breast cancer patients who harbor R273C mutation have worse overall survival than those with wild type TP53, but have better prognosis than those with R248W mutation. PMID 16489069 · Olivier et al., 2006 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID396In breast cancer patients harboring TP53 mutation, mutations in DNA contact regions such as R273 are prognostic for a worse relapse-free survival compared to other non-silent mutations in TP53. PMID 9569050 · Berns et al., 1998 · Open in CIViC | civic |
| Cisplatin + Etoposide + MitomycinCombination | Gastric CarcinomaALIAS | Predictive | C | Does Not Support | ||||
| TP53 G245S + TP53 R213* + TP53 R273C1 | ||||||||
| Pazopanib + VorinostatCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID12732In the phase I study of pazopanib and vorinostat in 36 patients with advanced solid tumors, detection of hotspot TP53 mutation was associated with a higher rate of SD ≥6 months/PR, longer median PFS (… (full text at CIViC) PMID 25669829 · Fu et al., 2015 · Open in CIViC | civic |
| TP53 R273H6 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID397Breast cancer patients who harbor R273H mutation have worse overall survival than those with wild type TP53, but have better prognosis than those with R248W mutation. PMID 16489069 · Olivier et al., 2006 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID398In breast cancer patients harboring TP53 mutation, mutations in DNA contact regions such as R273 are prognostic for a worse relapse-free survival compared to other non-silent mutations in TP53. PMID 9569050 · Berns et al., 1998 · Open in CIViC | civic |
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 4 | submitted | ||
Data updated 18 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| B |
| Supports Resistance |
| 3 |
| accepted |
EID3013In a study involving patients with invasive ovarian carcinoma who had undergone surgery, a subset of 73 patients were classified via response to platinum-based chemotherapy as sensitive or resistant/r… (full text at CIViC) PMID 11595686 · Reles et al., 2001 · Open in CIViC |
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| Cisplatin + Etoposide + MitomycinCombination | Malignant Gastric Neoplasm | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID2799In a Phase II trial of 25 patients with metastaic gastric cancer, patients received preoperative high dose chemotherapy (HDCT) consisting of etoposide, cisplatin and mitomycin. Patients with greater t… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| 2 |
| submitted |
EID6932In the evaluation of 275 oligodendroglial tumors, the specific genotype at amino acid 72 of TP53 (Arg/Arg, Arg/Pro, or Pro/Pro) was not associated grade of malignancy (low- vs. high-grade, P = 0.650) … (full text at CIViC) PMID 17854663 · Idbaih et al., 2007 · Open in CIViC |
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| 2 |
| submitted |
EID7429A preclinical study was testing the neomorphic effects of TP53-R175H mutation. Multiple human endometrial cancer KLE cell lines were categorized into different groups: Untransfected cells, Vector (ve… (full text at CIViC) PMID 19917135 · Dong et al., 2009 · Open in CIViC |
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| Doxorubicin | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID319Breast tumors in a mouse model with R172H mutation (homologous to human R175H) are more responsive to doxorubicin than breast tumors with wild type TP53. PMID 22698404 · Jackson et al., 2012 · Open in CIViC | civic |
| EAP Protocol | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | — | accepted | EID2310In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID4880Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID10074Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
In mouse models, the R248Q variant had accelerated onset of all tumor types and accelerated death rate. Endogenous R248Q proteins are devoid of several important wildtype tp53 tumor-suppressor functio… (full text at CIViC)
PMID 23538418 · Hanel et al., 2013 · Open in CIViC
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| (oncogenic) | Malignant Lung Neoplasm | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID7162R248Q increases in vitro invasiveness of human lung cancer NCI-H1299 cells. High potential to invade type 1 collagen gel (Fig.3) The variant lacks sequence-specific DNA binding and inhibits transactiv… (full text at CIViC) PMID 21187651 · Yoshikawa et al., 2010 · Open in CIViC | civic |
| Doxorubicin + Etoposide + PaclitaxelSequential | Malignant Ovarian Neoplasm | Predictive | D | Supports Resistance | 4 | submitted | EID7175Most common oncomorphic TP53 mutations are at positions R273, R248, R175, and Y220. Mutant R248Q confers chemoresistance to doxorubicin and paclitaxel. In vitro studies, cells with oncomorphic p53 de… (full text at CIViC) PMID 24065105 · Brachova et al., 2013 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID3042Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| 4 |
| accepted |
EID4879Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC |
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| 3 |
| accepted |
EID2292A female patient taking part in a 25 patient gastric cancer trial was diagnosed at age 46, and received preoperative high dose chemotherapy (HDCT). Japanese Society for Gastric Cancer Response Score w… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC |
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| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4881Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
EID7121Plasmids harboring human TP53 with or without an R273H mutation were stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression.… (full text at CIViC) PMID 8099841 · Dittmer et al., 1993 · Open in CIViC |
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| Doxorubicin + MethotrexateSubstitutes | Osteosarcoma | Predictive | D | Supports Resistance | 3 | accepted | EID7430Several preclinical studies were testing drug resistance mechanisms of TP53-R273H variant. Saos-2 cells were transfected with TP53-R273H mutation and these cells were used in the study. Using a wester… (full text at CIViC) PMID 17363498 · Wong et al., 2007 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4882Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| Tamoxifen | Malignant Breast Neoplasm | Predictive | C | Supports Resistance | — | submitted | EID2289In a study 202 breast cancer patients undergoing tamoxifen treatment, a higher frequency of wildtype TP53 patients responded to treatment compared to those with mutations in TP53 (66% wild-type vs. 31… (full text at CIViC) PMID 10786679 · Berns et al., 2000 · Open in CIViC | civic |