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 R273H1 | ||||||||
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID7980The glioblastoma U138 cell line possesses a TP53 R273H variant. This cell line initially exhibited resistance to temozolomide treatment, but a four-fold increase in chemosensitivity (IC50 127.79 ug/ml… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| TP53 R273L1 | ||||||||
| Carboplatin + CisplatinSubstitutes | Malignant Ovarian Neoplasm | Predictive | C | Supports Resistance | — | accepted | EID2286Ovarian cancer patients with TP53 missense mutations were refractory to platinum-based chemotherapy (66% vs. 34% in wildtype, P=0.008) and had a shorter time to disease progression (n=54, P=0.037). A … (full text at CIViC) PMID 11595686 · Reles et al., 2001 · Open in CIViC | civic |
| TP53 R280K1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4889Subset 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 R280T1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4890Subset 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 R282L1 | ||||||||
| EAP Protocol | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | — | accepted | EID2818In 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 R72P1 | ||||||||
| (predisposing) | Malignant Breast Neoplasm | Predisposing | B | Does Not Support Predisposition | 4 | accepted | EID1302Large meta-analysis of 5,191 breast cancer patients and 3,834 controls did not find a conclusive link between codon 72 allele and breast cancer susceptibility. Odds ratios were 0.98 (95% CI, 0.91–1.05… (full text at CIViC) PMID 17909070 · Schmidt et al., 2007 · Open in CIViC | civic |
| TP53 Rearrangement2 | ||||||||
| (diagnostic) | Osteosarcoma | Diagnostic | B | Supports Positive | 5 | submitted | EID9247Intron 1 rearrangements of TP53 were identified in 46 of 288 osteosarcoma cases (16%). No fusions were detected in 1090 other tumors screened. Fusions were associated with loss of TP53 expression. PMID 25762628 · Ribi et al., 2015 · Open in CIViC | civic |
| 〃 | Osteosarcoma | Diagnostic | B | Supports Positive | 4 | submitted | EID9248TP53 fusions were identified in 10 of 25 osteosarcoma cases. The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. PMID 26672768 · Lorenz et al., 2016 · Open in CIViC | civic |
| TP53 Truncating Mutation2 | ||||||||
| (prognostic) | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID525In patients with head and neck squamous cell carcinoma, in a multivariate analysis those with truncating mutations in TP53 had worse progression-free and overall survival than wild-type patients. PMID 21467160 · Lindenbergh-van der Plas et al., 2011 · Open in CIViC | civic |
| 〃 | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Does Not Support Poor Outcome | 4 | accepted | EID526In patients with head and neck squamous cell carcinoma, when comparing patients with any mutation in TP53 to wild-type, there was not a significant difference in overall survival in a multivariate ana… (full text at CIViC) PMID 21467160 · Lindenbergh-van der Plas et al., 2011 · Open in CIViC | civic |
| TP53 V143A3 | ||||||||
| (diagnostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Diagnostic | C | Supports N/A | 2 | submitted | EID2890TP53 mutations were identified in 38/80 colorectal cancer subjects at a Taiwanese hospital. One patient harbored the V143A mutation, and the authors note this is the first identification of V143A in c… (full text at CIViC) PMID 12795343 · Chang et al., 2003 · Open in CIViC | civic |
| 〃 | Lymphoplasmacytic Lymphoma | Diagnostic | C | Supports N/A | 2 | submitted | EID2891A 73 y.o. male with Waldenström's Macroglobulinemia, a rare type of non-Hodgkin's lymphoma, donated bone marrow upon cancer recurrence to establish the cell line MWCL1. The bone marrow was initially … (full text at CIViC) PMID 21415268 · Hodge et al., 2011 · Open in CIViC | civic |
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | |||||
| TP53 V157D1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9784A lung cancer patient was found to have TP53 V157D and PMS2 R20Q mutations in tumor tissue and distant normal lung tissue. These germline mutations were expressed alone or in combination in A549 lung … (full text at CIViC) PMID 23981578 · Wang et al., 2014 · Open in CIViC | civic |
| TP53 V157F1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4887Subset 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 V197E1 | ||||||||
| (predisposing) | Esophageal Squamous Cell CarcinomaALIAS | Predisposing | C | Supports Predisposition | 1 | submitted | EID9846Analysis of 77 esophageal squamous cell carcinoma tumor and normal samples for germline mutations revealed a rare TP53 V197E variant in a single patient. The V197E mutation is in the DNA-binding domai… (full text at CIViC) PMID 30833958 · Deng et al., 2019 · Open in CIViC | civic |
| TP53 Wildtype6 | ||||||||
| Adjuvant Chemotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1149Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA, 1209 patients, median follow-up 5.5 years) of platinum-based adjuvant chemotherapy (ACT) vers… (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC | civic |
| Capecitabine + Cetuximab + OxaliplatinCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID875In this retrospective biomarker analysis of the EXPERT-C trial, patients with TP53 wild-type status had a statistically significant better progression free survival (PFS) (89.3% vs 65.0% at 5 years; h… (full text at CIViC) PMID 24957073 · Sclafani et al., 2014 · Open in CIViC | civic |
| TP53 Y220C5 | ||||||||
| Bortezomib | Malignant Breast Neoplasm | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID6172TP53 Y220C is known to destabilize p53 and down-regulate p53-mediated apoptosis. The success of bortezomib may be explained by the previously reported up-regulation of caspase-mediated apoptosis, whic… (full text at CIViC) PMID 28679691 · Meißner et al., 2017 · Open in CIViC | civic |
| Cisplatin + Etoposide + MitomycinCombination | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID2306A male patient taking part in a 25 patient gastric cancer trial was diagnosed at age 50, harbored a TP53 mutation and received preoperative high dose chemotherapy (HDCT). Japanese Society for Gastric … (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant Neoplasm | |||||||
| TP53 Y234C1 | ||||||||
| Carboplatin + CisplatinSubstitutes | Malignant Ovarian Neoplasm | Predictive | C | Supports Resistance | — | accepted | EID2745Ovarian cancer patients with TP53 missense mutations were refractory to platinum-based chemotherapy (66% vs. 34% in wildtype, P=0.008) and had a shorter time to disease progression (n=54, P=0.037). A … (full text at CIViC) PMID 11595686 · Reles et al., 2001 · Open in CIViC | civic |
| NTRK1 Fusion9 | ||||||||
| Entrectinib | Malignant Ovarian Neoplasm | Predictive | C | Does Not Support Resistance | 2 | submitted | EID1174356-year-old women was diagnosed with a stage IV ovarian cancer. Debulking surgery, and chemotherapy was given for 10 months. However, disease recurred and at this time NGS was performed which detected… (full text at CIViC) PMID 35251641 · Endo et al., 2022 · Open in CIViC | civic |
| 〃 | Myofibroma | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID11861In a phase 1/2 trial of entrectinib in pediatric patients, tumors with fusions in NTRK, ROS1, or ALK had an overall response (ORR) of 57.7% (95% CI; 36.9-76.7). This included a patient with infantile… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | D | Supports | ||||
| ALK Fusion1 | ||||||||
| Lorlatinib | Inflammatory Myofibroblastic Tumor | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11293This case study was on a 40-year-old male with dyspnea and a productive cough. He was found to have a right upper lobe opacity on a chest X-ray. Subsequent investigations, including CT and PET, showed… (full text at CIViC) PMID 32868646 · Wong et al., 2020 · Open in CIViC | civic |
| JAK2 Fusion1 | ||||||||
| (diagnostic) | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | C | Supports Positive | 3 | accepted | EID7675In the study involving 1725 B-ALL patients, 264 were identified by microarray-based algorithm to have a Ph-like expression signature. Next generation sequencing (RNAseq, WGS, and/or WES) performed on … (full text at CIViC) PMID 25207766 · Roberts et al., 2014 · Open in CIViC | civic |
| NTRK1 Fusion9 | ||||||||
| (oncogenic) | NTRK-Rearranged Spindle Cell NeoplasmALIAS | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID11704An intra-chromosomal TPR::NTRK1 fusion was found in a superficial soft tissue tumor located on the hand of a 7-year-old girl. The tumor had a prominently infiltrative growth pattern reminiscent of lip… (full text at CIViC) PMID 27259011 · Agaram et al., 2016 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID11705A male child (1 year old) presented with a rapidly growing tumor in the cervical region that had been present for 2 months. It was a firm to hard soft-tissue mass. Radiologic imaging disclosed a tumor… (full text at CIViC) PMID 32489127 · Rekhi et al., 2021 · Open in CIViC | civic |
| Entrectinib | High-Grade Glioma, NOS | Predictive | ||||||
| TPT1 Overexpression1 | ||||||||
| Sertraline | Melanoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID5999TPT1(TCTP) overexpression was detected in several tumour types and silencing of TPT1 was shown to induce tumour reversion. There is a reciprocal repression between TPT1 and P53. Sertraline interacts w… (full text at CIViC) PMID 28751755 · Boia-Ferreira et al., 2017 · Open in CIViC | civic |
| BRAF Fusion1 | ||||||||
| Trametinib | Melanoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID727A TRIM24-BRAF fusion was identified in a single patient with metastatic melanoma that was "pan-negative" for driver mutations. A cell-line (293H) ectopically expressing the TRIM24-BRAF fusion was foun… (full text at CIViC) PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC | civic |
Data updated 17 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.
| Supports Oncogenicity |
| 3 |
| submitted |
EID7118Human mutant V143A 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 |
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| Chemotherapy | Esophageal Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID906Patients with p53 wild type (as defined by low expression and/or wild-type tp53 gene) had a higher response rate to chemotherapy-based treatment (total major response [MR]: risk ratio [RR] = 1.09, 95 … (full text at CIViC) PMID 23515910 · Zhang et al., 2013 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID2964MDM2 Inhibitor screen in a panel of 260 cancer cell lines with well characterized TP53 status shows that only cancer cell lines with unaltered TP53 may be sensitive to MDM2 Inhibitor. PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| Rebemadlin | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID2963MDM2 Inhibitor Nutlin-3a induced senescence in presence of functional TP53 in murine primary fibroblasts, oncogenically transformed fibroblasts, and fibrosarcoma cell lines. Cells lacking functional T… (full text at CIViC) PMID 17671205 · Efeyan et al., 2007 · Open in CIViC | civic |
| RG7112 | Leukemia | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2965Phase I Trial of RG7112 in 116 heavily pretreated patients with AML, ALL, CML, CLL, sCLL demonstrated sustained clinical improvement and induction of TP53 target genes in subset of patients with wild … (full text at CIViC) PMID 26459177 · Andreeff et al., 2016 · Open in CIViC | civic |
| Predictive |
| D |
| Supports Resistance |
| 4 |
| accepted |
EID4884Subset 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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| Rezatapopt | Malignant NeoplasmALIAS | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12297Rezatapopt demonstrated clinical efficacy in the PYNNACLE Phase 1 dose-escalation study (NCT04585750), showing promising responses in two heavily pre-treated patients with solid tumors. A patient with… (full text at CIViC) PMID 39945593 · Puzio-Kuter et al., 2025 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12296Four TP53 reactivator compounds—PC09859, PC10709, PC14374, and rezatapopt (PC14586)—were tested for their ability to restore wild-type (WT) TP53 function in TP53 Y220C-mutated cells. ELISA assays in N… (full text at CIViC) PMID 39945593 · Puzio-Kuter et al., 2025 · Open in CIViC | civic |
| 2 |
| accepted |
EID10094BaF3 cells transduced with a number of NTRK fusions demonstrated sensitivity to entrectinib. IC50 values were measured from cell viability assays (Cell Titer Glo) following 72-hour incubation with ent… (full text at CIViC) PMID 26884591 · Drilon et al., 2016 · Open in CIViC |
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| Larotrectinib | Sarcoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID6101Four patients with infantile fibrosarcoma and soft tissue sarcoma and a TPM3::NTRK1 fusion were treated with larotrectinib. All four patients had a partial or complete response in the target lesion. T… (full text at CIViC) PMID 29606586 · Laetsch et al., 2018 · Open in CIViC | civic |
| 〃 | Spindle Cell Sarcoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7419In a pediatric phase 1 trial (NCT02637687), a 12-year-old boy with TPM3-NTRK1 fusion was treated with Larotrectinib as first line treatment as no standard treatment options were available. Following a… (full text at CIViC) PMID 30204247 · DuBois et al., 2018 · Open in CIViC | civic |
| 〃 | Thyroid Gland Papillary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID8042A healthy 12 year old with right neck mass was found to have heterogeneous solid mass originating from the right thyroid lobe. Total thyroidectomy confirmed papillary thyroid carcinoma (PTC) with mult… (full text at CIViC) PMID 29610391 · Ronsley et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID11692The goal of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. This was achieved by reviewing data from two global, multicenter clinic… (full text at CIViC) PMID 35085007 · Drilon et al., 2022 · Open in CIViC | civic |
| Larotrectinib + LestaurtinibSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID978NTRK1 fusions (one LMNA-NTRK1 and two TPM3-NTRK1) were identified in 2% of Korean colorectal cancer patients (147 patients). TrkA (NTRK1) protein expression was associated with presence of NTRK1 gene … (full text at CIViC) PMID 26716414 · Park et al., 2016 · Open in CIViC | civic |
| Larotrectinib Regimen | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11703This was a Phase 1/2 study in which 55 patients between 4 months and 76 years of age with TRK-fusion positive tumors were given NTRK inhibitor Larotrectinib. Patients had 17 unique NTRK fusion type… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| C |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID11851In a phase 1/2 trial of entrectinib in pediatric patients, tumors with fusions in NTRK, ROS1, or ALK had an overall response (ORR) of 57.7% (95% CI; 36.9-76.7). This included one patient (4 yo) with … (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC |
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| Larotrectinib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID11706A female patient, 43 presented with right lower quadrant pain, and was surgically treated for perforated appendicitis including segmental small-bowel resection. Invasive adenocarcinoma stage IIB (pT4a… (full text at CIViC) PMID 35815302 · Kasi et al., 2022 · Open in CIViC | civic |
| 〃 | Gliosarcoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID11746A 9-month-old boy with no family history of cancer presented with increased head circumference, and MRI demonstrated a solid lesion in the left frontal lobe. A subtotal surgical resection was performe… (full text at CIViC) PMID 35034013 · Mançano et al., 2022 · Open in CIViC | civic |
| 〃 | Malignant Thyroid Gland Neoplasm | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID11748A 4.3-year-old girl had I-131–refractory papillary thyroid carcinoma (PTC). There was lymph node involvement and lung metastases. She underwent thyroidectomy and neck dissection, and administration of… (full text at CIViC) PMID 34237031 · Lee et al., 2021 · Open in CIViC | civic |
| 〃 | Solid NeoplasmCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID9589This Phase I study (NCT02122913) enrolled 70 heavily pretreated adult patients (median age 59.5 years) with various advanced solid tumors. Among them, one patient was identified with a TPR::NTRK1 fusi… (full text at CIViC) PMID 30624546 · Hong et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID11744In the clinical trial NCT01775072, one patient had TPR::NTRK1 positive non-small cell lung cancer, and had a partial response with larotrectinib treatment before eventual progression. PMID 33004339 · Cocco et al., 2021 · Open in CIViC | civic |
| 〃 | Thyroid Gland Papillary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID11747FFPE samples from 351 primary thyroid carcinomas were subjected to targeted gene rearrangement next-generation sequencing, and 11 NTRK rearrangements were found, all with intact kinase domains, and in… (full text at CIViC) PMID 32457407 · Chu et al., 2020 · Open in CIViC | civic |