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Profile Name TP53 wild-type
Gene Variant Detail

TP53 wild-type (no effect)

Relevant Treatment Approaches

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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
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...
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
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 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 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 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 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
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
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 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 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...
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
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
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
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
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 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
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 treatment demonstrated activity in patients with TP53 wild-type, MDM2-amplified dedifferentiated liposarcoma, resulting in a disease control rate (DCR) of 75% (9/12, all stable disease) and progression-free survival (PFS) ranging from 1.5 to 22 months, with PFS greater than 10.5 months in 41.6% (5/12) of patients (PMID: 37269344; NCT03449381). 37269344
MDM2 amp TP53 wild-type well-differentiated liposarcoma predicted - sensitive BI 907828 Phase I Actionable In a Phase I trial, BI 907828 treatment demonstrated activity in patients with TP53 wild-type, MDM2-amplified well-differentiated liposarcoma, resulting in a disease control rate of 100%, (7/7, 4 partial responses of at least 12 months, 3 stable disease), and a progression-free survival (PFS) of greater than 7.5 months, with a PFS of at least 14 months or more in 5 patients (PMID: 37269344; NCT03449381). 37269344
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 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 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 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 amp MDM2 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 with ALK and MDM2 amplification in culture (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 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 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 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 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
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 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 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
MDM2 pos TP53 wild-type triple-receptor negative breast cancer sensitive YX-02-030 Preclinical - Cell culture Actionable In a preclinical study, YX-02-030 decreased Mdm2 expression, increased apoptosis, decreased survival, and decreased mammosphere formation in TP53 wild-type triple-negative breast cancer cell lines in culture (PMID: 36734633). 36734633
EML4 - ALK MDM2 amp TP53 wild-type lung adenocarcinoma sensitive Milademetan + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination of Mekinist (trametinib) and Milademetan resulted in increased tumor growth inhibition compared to either therapy alone in a patient-derived xenograft model of lung adenocarcinoma harboring wild-type TP53, EML4-ALK, and MDM2 amplification (PMID: 37182602). 37182602
BRAF G469A MDM2 amp TP53 wild-type lung adenocarcinoma sensitive Milademetan + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mekinist (trametinib) and Milademetan synergistically inhibited proliferation in a lung adenocarcinoma cell line harboring BRAF G469A with wild-type TP53 and MDM2 amplification in culture (PMID: 37182602). 37182602
MDM2 amp TP53 wild-type heart sarcoma predicted - sensitive Milademetan Phase Ib/II Actionable In a Phase Ib/II trial, Milademetan treatment resulted in an overall response rate of 20% (2/10, both partial responses), a disease control rate of 60%, a median progression-free survival of 4.7 months, and a median overall survival of 12.2 months in patients with MDM2-amplified, TP53 wild-type intimal sarcoma (PMID: 37369013). 37369013
MDM2 amp TP53 wild-type Advanced Solid Tumor predicted - sensitive BI 907828 Phase I Actionable In a Phase I trial, BI 907828 treatment demonstrated safety and efficacy in patients with advanced solid tumors, resulting in a median progression-free survival of 8.1 months and an overall response rate of 11.1% (6/54, all partial responses (PR), 4 well-differentiated liposarcoma, 1 intrahepatic cholangiocarcinoma, 1 pancreatic cancer), with all PRs occurring in patients harboring an MDM2 amplification (PMID: 37269344; NCT03449381). 37269344
MDM2 amp TP53 wild-type glioblastoma sensitive BI 907828 Preclinical - Cell line xenograft Actionable In a preclinical study, BI 907828 treatment inhibited viability of a cell line derived from a TP53 wild-type, MDM2-amplified glioblastoma patient-derived xenograft (PDX) model in culture and inhibited tumor cell proliferation, induced apoptosis, and resulted in improved median survival compared to vehicle treatment (10 mg/kg treatment: 218 days and 2 mg/kg treatment: 57 days vs vehicle: 28 days, p<0.0001) in the PDX model, despite limited blood-brain barrier penetration (PMID: 37828724). 37828724
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