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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 |
|---|---|---|---|---|---|---|---|
| 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 R1275Q TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of TAE684 and Idasanutlin (RG7388) inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
| ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
| ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
| 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 F1174L TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Case Reports/Case Series | Actionable | In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture (PMID: 36602782). | 36602782 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture (PMID: 36602782). | 36602782 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
| 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 amp TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) resulted in an additive effect on tumor growth inhibition with complete remission in a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma with ALK amplification and overexpression (PMID: 36602782). | 36602782 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line with ALK amplification in culture (PMID: 36602782). | 36602782 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type, ALK-amplified neuroblastoma cell line in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
| 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 |
| 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 |
| ALK F1174C TP53 wild-type | neuroblastoma | resistant | Idasanutlin + Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma harboring ALK F1174C was resistant to combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) (PMID: 36602782). | 36602782 |
| ALK F1174V ALK amp TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). | 36602782 |
| ALK F1174V ALK amp TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). | 36602782 |
| TP53 wild-type VHL inact mut | renal cell carcinoma | sensitive | M8891 + Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, M8891 and Sutent (sunitinib) combination treatment resulted in improved tumor growth inhibition compared to monotherapies in patient-derived xenograft (PDX) models of TP53 wild-type renal cell carcinoma harboring VHL inactivating mutations (PMID: 37940144). | 37940144 |
| TP53 wild-type VHL inact mut | renal cell carcinoma | sensitive | Cabozantinib + M8891 | Preclinical - Pdx | Actionable | In a preclinical study, M8891 and Cometriq (Cabometyx, cabozantinib) combination treatment resulted in improved tumor growth inhibition compared to monotherapies in patient-derived xenograft (PDX) models of TP53 wild-type renal cell carcinoma harboring VHL inactivating mutations (PMID: 37940144). | 37940144 |
| TP53 wild-type VHL inact mut | renal cell carcinoma | sensitive | Axitinib + M8891 | Preclinical - Pdx | Actionable | In a preclinical study, M8891 and Inlyta (axitinib) combination treatment resulted in improved tumor growth inhibition compared to monotherapies in patient-derived xenograft (PDX) models of TP53 wild-type renal cell carcinoma harboring VHL inactivating mutations (PMID: 37940144). | 37940144 |