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| Gene | TP53 |
| Variant | L344R |
| Impact List | missense |
| Protein Effect | loss of function |
| Gene Variant Descriptions | TP53 L344R lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). L344R results in a decreased Tp53 tetramerization and transcriptional activity in cell culture (PMID: 19454241, PMID: 20505364). |
| Associated Drug Resistance | |
| Category Variants Paths |
TP53 mutant TP53 exon10 TP53 L344R TP53 mutant TP53 inact mut TP53 L344R |
| Transcript | NM_000546.6 |
| gDNA | chr17:g.7670678A>C |
| cDNA | c.1031T>G |
| Protein | p.L344R |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_001407264.1 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_000546.5 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001276760.3 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001276760.1 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001126112.3 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_000546.6 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001126118.1 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001407267.1 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001276761.3 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001407263.1 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001407265.1 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001126118.2 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001407266.1 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001126112 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_000546 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001276761.1 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001276761 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001407262.1 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001126112.2 | chr17:g.7670678A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001276760 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| NM_001126118 | chr17:g.7669643A>C | c.1031T>G | p.L344R | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 mutant | ovarian carcinoma | predicted - sensitive | Adavosertib | Case Reports/Case Series | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 4 of the patients achieved PR had ovarian carcinoma (OVC), and TP53 mutations were identified in 2 of the OVC patients with biopsies available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | glioblastoma | sensitive | AZD1390 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53 mutant glioblastoma cells demonstrated increased sensitivity to radiosensitization by AZD1390 treatment compared to TP53 wild-type cells in culture (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified IGF-1R antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Igf-1r antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | colorectal cancer | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | pharynx squamous cell carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a pharynx squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Ipilimumab + Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | medulloblastoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with aggressive disease in patients with SHH-activated medulloblastoma (NCCN.org). | detail... |
| TP53 mutant | sarcoma | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | esophagus squamous cell carcinoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment enhanced sensitivity of TP53-mutant esophageal squamous cell carcinoma cells to radiation therapy, resulting in decreased colony formation in culture (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus squamous cell carcinoma | predicted - sensitive | Adavosertib | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment inhibited viability of TP53-mutant esophageal squamous cell carcinoma cells in culture (PMID: 32220892). | 32220892 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified ERBB3 antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Erbb3 (Her3) antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | CG-806 | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived acute myeloid leukemia cells harboring TP53 mutations were sensitive to CG-806 in culture (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1323). | detail... |
| TP53 mutant | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | TP53 mutations except P47S and P72R are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
| TP53 mutant | colorectal cancer | sensitive | PD0166285 | Preclinical | Actionable | In a preclinical study, PD0166285 sensitizes colorectal cancer cells with TP53 mutation to radiation induced cell death (PMID: 11719452). | 11719452 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | esophagus adenocarcinoma | predicted - sensitive | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment inhibited phosphorylation of Wee1 and Cdk1, and reduced viability of TP53-mutant esophageal adenocarcinoma cells in culture, and led to partial tumor growth delay in cell line xenograft models (PMID: 32220892). | 32220892 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Obinutuzumab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is indicated in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation and for patients with relapsed or refractory disease after prior BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org). | detail... |
| TP53 mutant | endometrial carcinoma | predicted - sensitive | Adavosertib | Case Reports/Case Series | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 2 of the patients achieved PR had endometrial carcinoma (EC), and TP53 mutations were identified in 1 of the EC patients with biopsy available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | neuroblastoma | resistant | GSK2830371 | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutations were resistant to GSK2830371 induced growth inhibition in culture (PMID: 25658463). | 25658463 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | leukemia | decreased response | RG7112 | Phase I | Actionable | In a Phase I clinical trial, the majority of 19 leukemia patients with identified TP53 mutations did not demonstrate response to treatment with RG7112, with 2 acute myeloid leukemia patients harboring TP53 mutations showing clinical activity, but not improvement, and 1 sCLL/CLL patient achieving stable disease (PMID: 26459177). | 26459177 |
| TP53 mutant | neuroblastoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to nutlin-3 mediated growth inhibition (PMID: 21725357). | 21725357 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab | Guideline | Actionable | Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | lung non-small cell carcinoma | sensitive | CEP-8983 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of CEP-8983 and Platinol (cisplatin) worked synergistically to induce cell death in non-small cell lung cancer cell lines in culture, irrespective of TP53 status (PMID: 23428903). | 23428903 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Duvelisib | Guideline | Actionable | Copiktra (duvelisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | esophagus adenocarcinoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment enhanced sensitivity of TP53-mutant esophageal adenocarcinoma cells to radiation therapy, resulting in inhibition of phosphorylation of Wee1 and Cdk1, reduced colony formation, and increased DNA damage and mitotic cell death in culture, and tumor growth inhibition and regression in cell line xenograft models (PMID: 32220892). | 32220892 |
| TP53 mutant | ovarian cancer | no benefit | Nutlin-3a | Preclinical | Actionable | In a preclinical study, treatment with Nutlin-3 had little effect on growth of ovarian cancer cells with TP53 mutations in culture (PMID: 25964101). | 25964101 |
| TP53 mutant | tongue squamous cell carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a tongue squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 mutant | high grade glioma | predicted - sensitive | KU-60019 + Radiotherapy | Preclinical | Actionable | In a preclinical study, KU-60019 treatment increased sensitivity to radiotherapy in TP53-mutant mouse glioma cells in culture, and the combination prolonged survival in syngeneic intracranial tumor models compared to radiation alone (PMID: 29769307). | 29769307 |
| TP53 mutant | neuroblastoma | resistant | MI-63 | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to MI-63 mediated growth inhibition (PMID: 21725357). | 21725357 |
| TP53 mutant | ovarian serous carcinoma | sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment decreased mutant Tp53 level, resulted in apoptosis of ovarian serous carcinoma cells harboring TP53 mutations in culture (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is indicated in guidelines as first-line (category 2A), second-line, or third-line therapy (category 2B) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is included in guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | detail... 38969011 |
| TP53 mutant | colon carcinoma | predicted - sensitive | Camptothecin + CHIR-124 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant colon carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). | 17255282 |
| TP53 mutant | high grade glioma | no benefit | AZ31 + Radiotherapy | Preclinical | Actionable | In a preclinical study, AZ31 treatment increased sensitivity to radiotherapy in TP53-mutant mouse glioma cells in culture, but failed to radiosensitize tumors in syngeneic mouse models due to poor blood-brain barrier permeability (PMID: 29769307). | 29769307 |
| TP53 mutant | Advanced Solid Tumor | sensitive | CTX-1 | Preclinical | Actionable | In a preclinical study, CTX-1 induced increased Tp53 protein levels and cell death in human tumor cell lines with mutant Tp53 in culture (PMID: 26883273). | 26883273 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib | Guideline | Actionable | Zydelig (idelalisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | Advanced Solid Tumor | sensitive | Unspecified VEGFR inhibitor | Clinical Study - Cohort | Actionable | In a clinical study, VEGF/VEGFR inhibitor treatment resulted in improved rates of response (stable disease over 6 months/partial/complete response, 31% vs 7%), time-to-treatment failure, and overall survival (both p<0.01) compared to control in patients with TP53 mutant advanced solid tumors (n=106), but not in patients with TP53 wild-type tumors (n=82) (PMID: 27466356). | 27466356 |
| TP53 mutant | colorectal cancer | sensitive | Prodigiosin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 26759239). | 26759239 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Pirtobrutinib | Guideline | Actionable | Jaypirca (pirtobrutinib) is included in guidelines as second-line or third-line therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation and for patients with relapsed or refractory disease after prior BTK inhibitor and Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 mutant | glioblastoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and radiation therapy synergized to inhibit tumor growth in a human glioblastoma multiforme cell line xenograft model harboring mutant TP53 (PMID: 21992793). | 21992793 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib + Obinutuzumab | Guideline | Actionable | Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is indicated in the guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Rituximab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Alemtuzumab + Rituximab | Guideline | Actionable | Campath (alemtuzumab) combined with Rituxan (rituximab) is indicated in guidelines as therapy for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation who received prior treatment with a BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | ovarian cancer | predicted - sensitive | Adavosertib + Carboplatin | Phase II | Actionable | In a Phase II trial, Paraplatin (carboplatin) and Adavosertib (MK-1775) combination treatment resulted in an overall response rate of 43% (9/21), a median progression-free survival of 5.3 months and a median overall survival of 12.6 months in ovarian cancer patients harboring TP53 mutations (PMID: 27998224; NCT01164995). | 27998224 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) and Rituxan (rituximab) combination therapy is included in guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | detail... 38969011 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Lenalidomide + Rituximab | Guideline | Actionable | Revlimid (lenalidomide) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | sarcoma | sensitive | Pazopanib | Clinical Study - Cohort | Actionable | In a retrospective analysis, advanced sarcoma patients with TP53 mutations displayed improved progression-free survival (208 vs 136 days, p=0.036) relative to patients with wild-type TP53 when treated with Votrient (pazopanib) (PMID: 26646755). | 26646755 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is included in guidelines as preferred first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | 38969011 detail... |
| TP53 mutant | Advanced Solid Tumor | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) improved progression-free survival and overall survival in advanced solid tumor patients harboring TP53 hotspot mutations, and resulted in an increased stable disease rate of 45% (5/11), compared to a stable disease rate of 16% (4/25) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | Ibrutinib + Venetoclax | Phase II | Actionable | In a Phase II trial, Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy resulted in a response rate of 100% (14/14, 9 complete response, 5 partial response) in relapsed or refractory chronic lymphocytic leukemia (CLL) patients, and a response rate of 100% (16/16, 9 complete response, 7 partial response) in untreated patients with high-risk features including del 17p, TP53 mutations, and del 11q (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 429; NCT02756897). | detail... |
| TP53 mutant | Advanced Solid Tumor | resistant | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) did not inhibit growth of human tumor cell lines harboring TP53 mutations in culture (PMID: 25567130). | 25567130 |
| TP53 mutant | ovarian cancer | sensitive | Etoposide + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and etoposide worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). | 25964101 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) and Gazyva (obinutuzumab) combination therapy is included in guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | 38969011 detail... |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | Azacitidine + Hu5F9-G4 | Phase I | Actionable | In a Phase Ib trial, Magrolimab (Hu5F9-G4) and Vidaza (azacitidine) combination therapy was well tolerated, and resulted in complete response in 42% (5/12), complete response with incomplete hematologic recovery in 33% (4/12), and stable disease in 17% (2/12) of patients with acute myeloid leukemia harboring TP53 mutations and unfit for chemotherapy (J Clin Oncol 38: 2020 (suppl; abstr 7507); NCT03248479). | detail... |
| TP53 mutant | high grade glioma | predicted - sensitive | AZ32 + Radiotherapy | Preclinical | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in TP53 mutant mouse glioma cells, resulting in reduced cell survival and impaired DNA damage response in culture, and prolonged survival and significantly increased apoptosis of tumor cells compared to normal brain cells (p<0.01) in syngeneic intracranial tumor models (PMID: 29769307). | 29769307 |
| TP53 mutant | head and neck squamous cell carcinoma | predicted - sensitive | Buparlisib + Paclitaxel | Phase II | Actionable | In a Phase II (BERIL-1) trial, Buparlisib (BKM120) and Taxol (paclitaxel) combination treatment resulted in improved overall survival (HR=0.52) and prolonged progression-free survival (HR=0.45) in head and neck squamous cell carcinoma patients harboring TP53 mutations compared to TP53 wild-type patients (PMID: 29490986; NCT01852292). | 29490986 |
| TP53 mutant | ovarian cancer | predicted - sensitive | Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, Lynparza (olaparib) treatment inhibited tumor growth but did not induce regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring wild-type ATM and TP53 mutation (PMID: 31699977). | 31699977 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Rituximab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is indicated in the guidelines as first-line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | CG-806 | Case Reports/Case Series | Actionable | In a Phase I trial, CG-806 treatment was well-tolerated, and a patient with chronic lymphocytic leukemia harboring a TP53 mutation stayed on treatment for more than 8 cycles (25th Annual Congress of EHA (Jun 2020), Abstract EP711; NCT03893682). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is included in guidelines as preferred first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | detail... 38969011 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | predicted - sensitive | Zanubrutinib | Phase I | Actionable | In a Phase I trial, Brukinsa (zanubrutinib) treatment resulted in an overall response rate of 100% (16/16) in patients with CLL/SLL harboring del (17p) or TP53 mutations (PMID: 31340982; NCT02343120). | 31340982 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | predicted - sensitive | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is included in guidelines as first line therapy and second line therapy and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | Doxorubicin + Seliciclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, sequential administration of Roscovotine (seliciclib) followed by Adriamycin (doxorubicin) synergistically induced apoptosis in TP53-mutant triple-receptor negative breast cancer cell lines in culture, and inhibited tumor growth, prolonged survival in cell line xenograft models (PMID: 26826118). | 26826118 |
| TP53 mutant | Advanced Solid Tumor | predicted - sensitive | Adavosertib | Phase I | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a prtial response in 3 and progressive disease in 2 of 6 patients with advanced solid tumors harboring TP53 mutations (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | Advanced Solid Tumor | predicted - sensitive | Adavosertib | Phase I | Actionable | In a retrospective analysis of a Phase I trial, Adavosertib (MK-1775) combined with a chemotherapy resulted in a 21% (4/19) response rate in advanced solid tumor patients harboring a TP53 mutation and in those without a TP53 mutation, a 12% (4/33) response rate was observed (PMID: 27601554; NCT00648648). | 27601554 |
| TP53 mutant | breast cancer | sensitive | PK11007 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53-mutated breast cancer cell lines demonstrated increased sensitivity to PK11007 compared to TP53-wild type cells in culture, regardless of Esr1 and Erbb2 (Her2) status (J Clin Oncol 35, 2017 (suppl; abstr e14099)). | detail... |
| TP53 mutant | head and neck squamous cell carcinoma | sensitive | AZD7762 + Cisplatin | Preclinical | Actionable | In a preclinical study, the treatment of a head and neck squamous cell carcinoma cell line with mutant TP53 (C176F and A161S) with AZD7762, a pan Chk1/2 inhibitor, sensitizes the cells to Platinol (cisplatin) (PMID: 23839309). | 23839309 |
| TP53 mutant | B-cell acute lymphoblastic leukemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). | detail... |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, a retrospective analysis of a Phase I trial demonstrated non-small cell lung carcinoma (NSCLC) patients harboring either a TP53 mutation (n=15) or KRAS mutation (n=8) had greater progression free survival compared to NSCLC patients harboring wild-type TP53 or KRAS (n=15) (14.5mo vs 14.7mo vs 3.5mo, respectively) when treated with Keytruda (pembrolizumab) (PMID: 28039262). | 28039262 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | Carboplatin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, Nutlin-3 and Paraplatin (carboplatin) synergistically inhibited growth in TP53 mutated triple-receptor negative breast cancer cell lines in culture and in cell line xenograft models (PMID: 26494859). | 26494859 |
| TP53 mutant | acute myeloid leukemia | sensitive | Decitabine | Guideline | Actionable | Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | Duvelisib | Phase I | Actionable | In a Phase I trial, Copiktra (duvelisib) treatment inhibited Akt phosphorylation, resulted in complete response in 2% (1/49), partial response in 53% (26/49), and stable disease in 43% (21/49) of chronic lymphocytic leukemia patients, of which 49% (23/47) carried TP53 mutations (Blood 124 (21): 3334). | detail... |
| TP53 mutant | hypopharynx cancer | resistant | unspecified EGFR antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of two unspecified EGFR antibodies targeting nonoverlapping epitopes of Egfr did not inhibit proliferation of Tp53 mutated hypopharyngeal carcinoma cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with inferior leukemia-free survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| TP53 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| TP53 mutant | Advanced Solid Tumor | sensitive | Bevacizumab | Clinical Study - Cohort | Actionable | In a retrospective study, Avastin (bevacizumab) treatment was associated with increased progression-free survival in cancer patients carrying TP53 mutations (PMID: 23670029). | 23670029 |
| TP53 mutant | lung non-small cell carcinoma | not predictive | Osimertinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with non-small cell lung cancer harboring TP53 mutations at treatment discontinuation of Tagrisso (osimertinib) had shorter time to treatment discontinuation (6.5 vs 11.5 months, p=0.0029) compared to patients with wild-type TP53 (PMID: 31839416). | 31839416 |
| TP53 mutant | osteosarcoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing osteosarcoma (NCCN.org). | detail... |
| TP53 mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline TP53 mutations result in Li-Fraumeni syndrome, which is associated with increased risk of developing breast cancer (NCCN.org). | detail... |
| TP53 mutant | colorectal cancer | predicted - sensitive | NSC59984 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NSC59984 treatment resulted in increased Tp53 signaling and cell death in colorectal cancer cell lines harboring TP53 mutations, and inhibited tumor growth in TP53-mutant cell line colorectal cancer xenograft models (PMID: 26294215). | 26294215 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | GDC-0425 + Gemcitabine | Phase I | Actionable | In a Phase I trial, treatment with GDC-0425 followed by Gemzar (gemcitabine) resulted in a partial response in a patient with triple-receptor negative breast cancer harboring a TP53 mutation (PMID: 27815358). | 27815358 |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | Cytarabine + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 30% (3/10) of patients with acute myeloid leukemia harboring TP53 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). | detail... |
| TP53 mutant | glioblastoma | sensitive | Adavosertib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Adavosertib (MK-1775) decreased CDK1 phosphorylation and reduced tumor growth in patient-derived xenograft models of glioblastoma multiforme that harbor TP53 mutations (PMID: 27196784). | 27196784 |
| TP53 mutant | fibrous histiocytoma | predicted - sensitive | GDC-0575 + Gemcitabine | Preclinical - Pdx | Actionable | In a preclinical study, GDC-0575 and Gemzar (gemcitabine) combination treatment inhibited tumor growth, prolonged progression-free survival in patient-derived xenogrft (PDX) models of undifferentiated pleomorphic sarcoma (fibrous histiocytoma) (PMID: 29409053). | 29409053 |
| TP53 mutant | nephroblastoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing Wilms tumor (nephroblastoma) (NCCN.org). | detail... |
| TP53 mutant | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical | Actionable | In a preclinical study, ovarian clear cell adenocarcinoma cell lines harboring TP53 mutations demonstrated reduced sensitivity to DS-7423 induced apoptosis in culture compared to TP53 wild-type cells (PMID: 24504419). | 24504419 |
| TP53 mutant | acute myeloid leukemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org). | detail... |
| TP53 mutant | mantle cell lymphoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with poor prognosis in patients with mantle cell lymphoma who are treated with conventional therapy, including transplant (NCCN.org). | detail... |
| TP53 mutant | medulloblastoma | decreased response | JQ1 | Preclinical | Actionable | In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). | 24231268 |
| TP53 mutant | ovarian cancer | sensitive | AZD7648 | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of ovarian cancer harboring a TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified ERBB3 antibody + unspecified IGF-1R antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody, an unspecified Erbb3 (Her3) antibody, and an unspecified Igf-1r antibody resulted in potent inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | breast carcinoma | predicted - sensitive | Camptothecin + CHIR-124 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant breast carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). | 17255282 |
| TP53 mutant | ovarian cancer | predicted - sensitive | AZD7648 + Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 and Lynparza (olaparib) combination treatment induced tumor regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
| TP53 mutant | sarcoma | predicted - sensitive | GDC-0575 + Gemcitabine | Phase I | Actionable | In a Phase I trial, GDC-0575 and Gemzar (gemcitabine) combination treatment resulted in a prolonged tumor response in 2 soft tissue sarcoma patients harboring TP53 mutations, and no response in a patient with TP53 wild-type tumor (PMID: 29409053; NCT01564251). | 29409053 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is included in guidelines as preferred first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | 38969011 detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is indicated in the guidelines as first line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 inact mut | chronic lymphocytic leukemia | predicted - sensitive | AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 induced cell death in TP53-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132). | 26563132 |
| TP53 inact mut | prostate cancer | no benefit | Abiraterone | Clinical Study - Cohort | Actionable | In a clinical study, treatment with either Xtandi (enzalutamide) or Zytiga (abiraterone) in patients with metastatic castration-resistant prostate cancer harboring a TP53 inactivating mutation, detected via circulating tumor cells, demonstrated a shorter progression-free survival (3.0 vs 8.7mo; P<0.0001) and overall survival (7.8 vs 26.7mo; P<0.0001) and fewer patients with a PSA response greater than or equal to 50% (15.4 vs 46.8%; P=0.008) compared to those patients with wild-type TP53 (PMID: 30209161). | 30209161 |
| TP53 inact mut | prostate cancer | no benefit | Enzalutamide | Clinical Study - Cohort | Actionable | In a clinical study, treatment with either Xtandi (enzalutamide) or Zytiga (abiraterone) in patients with metastatic castration-resistant prostate cancer harboring a TP53 inactivating mutation, detected via circulating tumor cells, demonstrated a shorter progression-free survival (3.0 vs 8.7mo; P<0.0001) and overall survival (7.8 vs 26.7mo; P<0.0001) and fewer patients with a PSA response greater than or equal to 50% (15.4 vs 46.8%; P=0.008) compared to those patients with wild-type TP53 (PMID: 30209161). | 30209161 |
| TP53 inact mut | ovarian cancer | sensitive | Cisplatin + LB-100 | Preclinical | Actionable | In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in a cisplatin-resistant ovarian cancer cell line harboring a TP53 inactivating mutation in culture (PMID: 25376608). | 25376608 |
| TP53 inact mut | lung non-small cell carcinoma | not predictive | Osimertinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with non-small cell lung cancer harboring inactivating TP53 mutations at treatment discontinuation of Tagrisso (osimertinib) had shorter time to treatment discontinuation (5 vs 11.5 months, p=0.0005) compared to patients with wild-type TP53 (PMID: 31839416). | 31839416 |
| TP53 inact mut | ovarian carcinoma | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death and decreased proliferation of ovarian carcinoma cells harboring TP53 mutations in culture, but did not effect viability of ovarian carcinoma cells with wild-type TP53 (PMID: 26748848). | 26748848 |
| TP53 inact mut | breast cancer | sensitive | AMG 900 | Preclinical | Actionable | In a preclinical study, breast cancer cell lines with TP53 loss of function mutations had more pronounced apoptosis after treatment with AMG 900 in culture (PMID: 24091768). | 24091768 |
| TP53 inact mut | ovarian cancer | sensitive | Adavosertib + Carboplatin + Paclitaxel | Phase II | Actionable | In a Phase II trial, treatment with Adavosertib (MK-1775) plus Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in an improved progression-free survival by enhanced RECIST of 7.9 mo vs. 7.3 mo with placebo plus chemotherapy, and complete response in 11/9% (7/59) vs. 8.9% (5/62), partial response in 62.7% (37/59) vs. 61.3% (38/62), and stable disease in 5.1% (3/59) vs. 4.8% (3/62) of patients with platinum-sensitive ovarian cancer harboring an inactivating TP53 mutation (PMID: 32611648; NCT01357161). | 32611648 |
| TP53 inact mut | lung small cell carcinoma | sensitive | APR-246 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, APR-246 induced apoptosis in small-cell lung cancer (SCLC) cell lines and decreased tumor growth in SCLC cell line xenograft models harboring Tp53 inactivating mutations (PMID: 21415220). | 21415220 |
| TP53 inact mut | breast carcinoma | predicted - sensitive | CHIR-124 + Irinotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, sequential treatment with Camptosaur (irinotecan) and CHIR-124 enhanced tumor growth inhibition compared to either agent alone in a breast carcinoma cell line xenograft model with defective TP53 (PMID: 17255282). | 17255282 |
| TP53 inact mut | breast cancer | sensitive | Adavosertib + Radiotherapy | Preclinical | Actionable | In a preclinical study, Adavosertib (MK-1775) increased the efficacy of radiation in breast cancer cells with defective TP53 in culture (PMID: 21799033). | 21799033 |
| TP53 inact mut | breast carcinoma | predicted - sensitive | CHIR-124 + SN-38 | Preclinical - Cell culture | Actionable | In a preclinical study, SN-38 and CHIR-124 demonstrated synergy in a breast carcinoma cell line with defective TP53, resulting in increased cell cycle arrest and apoptosis in culture (PMID: 17255282). | 17255282 |
| TP53 inact mut | chronic lymphocytic leukemia | sensitive | Ceralasertib + Ibrutinib | Preclinical | Actionable | In a preclinical study, AZD6738 sensitized TP53-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132). | 26563132 |
| TP53 inact mut | ovarian cancer | sensitive | Cisplatin + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and cisplatin worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). | 25964101 |