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| Gene | TP53 |
| Variant | wild-type |
| Impact List | none |
| Protein Effect | no effect |
| Gene Variant Descriptions | Wild-type TP53 indicates that no mutation has been detected within the TP53 gene. |
| Associated Drug Resistance | |
| Category Variants Paths |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| MDM2 amp TP53 wild-type | osteosarcoma | sensitive | KRT-232 | Preclinical | Actionable | In a preclinical study, KRT-232 (AMG 232) inhibited tumor growth in osteosarcoma cell line xenograft models with wild-type TP53 and MDM2 amplification (PMID: 25567130, PMID: 24967612). | 24967612 25567130 |
| MDM2 amp TP53 wild-type | osteosarcoma | sensitive | SAR405838 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR405838 inhibited growth of TP53 wild-type, MDM2 amplified osteosarcoma in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). | 25145672 |
| MDM2 amp TP53 wild-type | osteosarcoma | sensitive | Doxorubicin + KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of KRT-232 (AMG 232) and Adriamycin (doxorubicin) inhibited tumor growth and induced tumor regression in an MDM2-amplifed TP53 wild-type osteosarcoma cell line xenograft model, with increased efficacy over either agent alone (PMID: 25567130). | 25567130 |
| MDM2 amp TP53 wild-type | liposarcoma | sensitive | SAR405838 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR405838 decreased viability and induced cell cycle arrest in MDM2-amplified dedifferentiated liposarcoma cell lines with wild-type TP53 in culture, and induced TP53 pathway activation and tumor regression in xenograft models (PMID: 26475335). | 26475335 |
| MDM2 amp TP53 wild-type | glioblastoma | sensitive | RG7112 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, glioblastoma multiforme (GBM) cell lines with amplification of MDM2 and wild-type TP53 demonstrated sensitivity to RG7112 in culture, resulting in decreased viability and restoration of Tp53 signaling, and treatment with RG7112 resulted in growth inhibition in MDM2-amplified TP53 wild-type GBM cell line xenograft models (PMID: 26482041). | 26482041 |
| MDM2 amp TP53 wild-type | glioblastoma | predicted - sensitive | KRT-232 | Phase I | Actionable | In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 60% (6/10) of patients with TP53 wild-type, MDM2 amplified glioblastoma, with a median duration of 1.8 months (PMID: 31359240; NCT01723020). | 31359240 |
| MDM2 amp TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | KRT-232 | Phase I | Actionable | In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 62.5% (10/16) of patients with TP53 wild-type, MDM2 amplified solid tumors other than liposarcoma, glioblastoma, and breast cancer, with a median duration of 3.3 months, and a patient with squamous cell carcinoma achieved unconfirmed partial response per central evaluation (PMID: 31359240; NCT01723020). | 31359240 |
| MDM2 amp TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | ALRN-6924 | Phase I | Actionable | In a Phase I trial, treatment with ALRN-6924 resulted in a disease control rate of 71% (5/7) in advanced solid tumors patients with wild-type TP53 and MDM2 amplification (PMID: 34301750; NCT02264613). | 34301750 |
| MDM2 amp TP53 wild-type | dedifferentiated liposarcoma | predicted - sensitive | BI 907828 | Phase I | Actionable | In a Phase I trial, BI 907828 demonstrated activity in patients with TP53 wild-type, MDM2-amplified tumors, including a disease control rate (DCR) of 93% and progression-free survival greater than 10.5 months (PFS>10.5) in 5 of 11 dedifferentiated liposarcoma patients, a DCR of 88% and PFS>10.5 months in 4 of 8 well-differentiated liposarcoma patients (Ann Oncol (2022) 33 (suppl_7): S197-S224; NCT03449381). | detail... |
| MDM2 amp TP53 wild-type | well-differentiated liposarcoma | predicted - sensitive | BI 907828 | Phase I | Actionable | In a Phase I trial, BI 907828 demonstrated activity in patients with TP53 wild-type, MDM2-amplified tumors, including a disease control rate (DCR) of 93% and progression-free survival greater than 10.5 months (PFS>10.5) in 5 of 11 dedifferentiated liposarcoma patients, a DCR of 88% and PFS>10.5 months in 4 of 8 well-differentiated liposarcoma patients (Ann Oncol (2022) 33 (suppl_7): S197-S224; NCT03449381). | detail... |
| BRAF mut TP53 wild-type | melanoma | sensitive | CGM097 + Encorafenib | Preclinical | Actionable | In a preclinical study, the combination of CGM097 and Encorafenib (LGX818) synergized to inhibit cell growth of a human melanoma cell line harboring mutant BRAF and wild-type TP53 in culture, and promoted tumor regression in xenograft models (Cancer Res October 1, 2014 74; 5466). | detail... |
| BRAF mut TP53 wild-type | melanoma | sensitive | KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). | 25567130 |
| BRAF mut TP53 wild-type | colorectal cancer | sensitive | CGM097 + Dabrafenib + Navitoclax + PF-04217903 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 |
| BRAF mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |
| RB1 wild-type TP53 wild-type | breast carcinoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | colon carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | lung carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of lung carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | melanoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of melanoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | mantle cell lymphoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). | 17121911 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). | 26438783 |
| ALK wild-type MDM2 amp TP53 wild-type | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK, wild-type TP53, and MDM2 amplification (PMID: 26438783). | 26438783 |
| ALK F1245C TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Pdx | Actionable | In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). | 26438783 |
| ALK act mut TP53 wild-type | neuroblastoma | predicted - sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). | 26438783 |
| ALK mut TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). | 26438783 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 wild-type | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). | 26438783 |
| BRAF V600E PIK3CA H1047R TP53 wild-type | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell culture | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture (PMID: 26272063). | 26272063 |
| BRAF V600E PTEN loss TP53 wild-type | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). | 26272063 |
| MDM2 over exp TP53 wild-type | neuroblastoma | sensitive | MX69 | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line over expressing MDM2 and wild-type for TP53 demonstrated sensitivity to treatment with MX69 in culture, resulting in decreased cell survival (PMID: 27666947). | 27666947 |
| MDM2 over exp TP53 wild-type | acute lymphoblastic leukemia | sensitive | MX69 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MX69 treatment induced cell death and inhibited cell growth in a TP53 wild-type acute lymphocytic leukemia cell line over expressing MDM2, and prolonged survival in xenograft models (PMID: 27666947). | 27666947 |
| MDM2 over exp TP53 wild-type | osteosarcoma | sensitive | RO6839921 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RO6839921 demonstrated anti-tumor activity in TP53 wild-type, MDM2 over-expressing osteosarcoma cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). | detail... |
| MDM2 over exp TP53 wild-type | acute lymphoblastic leukemia | sensitive | AQ-101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AQ-101 inhibited growth and induced apoptosis in acute lymphocytic leukemia (ALL) cell lines with wild-type TP53 and overexpression of MDM2 in culture, and inhibited development of leukemia in ALL cell line xenograft models (PMID: 29282301). | 29282301 |
| MDM2 over exp TP53 wild-type | ovarian clear cell carcinoma | predicted - sensitive | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) treatment sensitized ovarian clear cell carcinoma cell lines harboring wild-type TP53 and MDM2 overexpression to T-cell mediated killing when co-cultured with T-cells, demonstrating decreased cell viability (PMID: 32655895). | 32655895 |
| MDM2 over exp TP53 wild-type | ovarian clear cell carcinoma | predicted - sensitive | KRT-232 + Pembrolizumab | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian clear cell carcinoma cell line harboring wild-type TP53 and MDM2 overexpression was sensitive to combination treatment with KRT-232 (AMG 232) and Keytruda (pembrolizumab) when co-cultured with T cells, demonstrating increased T-cell mediated cell death (PMID: 32655895). | 32655895 |
| NRAS mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |