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Gene | MDM2 |
Variant | amp |
Impact List | none |
Protein Effect | no effect |
Gene Variant Descriptions | MDM2 amp indicates an increased number of copies of the MDM2 gene. However, the mechanism causing the increase is unspecified. |
Associated Drug Resistance | |
Category Variants Paths |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MDM2 amp | neuroendocrine tumor | predicted - sensitive | Milademetan | Case Reports/Case Series | Actionable | In a Phase I trial, Milademetan demonstrated safety and preliminary activity in patients with advanced solid tumors, and resulted in prolonged stable disease in 2 patients with MDM2-amplified tumors, 1 with liposarcoma and 1 with carcinoid tumor (J Clin Oncol 34, 2016 (suppl; abstr 2581; NCT01877382). | detail... |
MDM2 amp | urinary bladder cancer | no benefit | Atezolizumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic bladder cancer that harbored MDM2 amplification and other mutations quickly progressed after receiving Tecentriq (atezolizumab), resulting in new liver metastasis and a 258% increase of existing liver metastasis size 1.9 months after treatment (PMID: 28351930). | 28351930 |
MDM2 amp | triple-receptor negative breast cancer | no benefit | Pembrolizumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with triple-receptor negative breast cancer that harbored MDM2 amplification quickly progressed after receiving Keytruda (pembrolizumab), resulted in new chest wall metastasis and a 55% increase of existing lung metastasis size 1.5 months after treatment (PMID: 28351930). | 28351930 |
MDM2 amp | endometrial stromal sarcoma | no benefit | Nivolumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with endometrial stromal sarcoma that harbored MDM2 amplification quickly progressed after receiving Opdivo (nivolumab), resulted in new abdominal metastasis and a 242% increase of existing liver metastasis size within 1.5 months of treatment (PMID: 28351930). | 28351930 |
MDM2 amp | Advanced Solid Tumor | no benefit | N/A | Clinical Study | Emerging | In a clinical study, 100% (5/5) of solid tumor patients harboring MDM2 amplification experienced disease progression within 2 months of anti-PD1/PD-L1 monotherapy, indicating a risk for hyperprogression on immunotherapy (PMID: 28351930). | 28351930 |
MDM2 amp | liposarcoma | predicted - sensitive | GDC-0575 + Gemcitabine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GDC-0575 and Gemzar (gemcitabine) synergistically induced apoptosis and cell cycle arrest in liposarcoma cells harboring MDM2 amplification in culture, and inhibited tumor growth, prolonged progression-free survival in cell line xenogrft models (PMID: 29409053). | 29409053 |
MDM2 amp | liposarcoma | predicted - sensitive | unspecified MDM2 inhibitor | Phase I | Actionable | In a Phase I trial, treatment with an unspecified MDM2 inhibitor resulted in clinical efficacy in six patients with liposarcoma harboring MDM2 amplification, including three patients with a partial response and two patients with stable disease for 15.7 months and 4.7 months (PMID: 30237864). | 30237864 |
MDM2 amp | dedifferentiated liposarcoma | predicted - sensitive | BI 907828 | Preclinical - Pdx | Actionable | In a preclinical study, BI 907828 treatment resulted in tumor regression in patient-derived xenograft (PDX) models of dedifferentiated liposarcoma harboring MDM2 amplification (PMID: 31201607). | 31201607 |
MDM2 amp | liposarcoma | predicted - sensitive | BI 907828 | Case Reports/Case Series | Actionable | In a Phase I trial, BI 907828 treatment led to a partial response in 3 of 7 patients with liposarcoma, all responders harbored MDM2 amplification (Ann Oncol 32 (2021): S1294; NCT03449381). | detail... |
MDM2 amp | dedifferentiated liposarcoma | sensitive | Milademetan | Phase I | Actionable | In a Phase I trial, Milademetan treatment resulted in an objective response rate of 3.8% (2/53, 2 partial responses), a disease control rate of 58.5%, and a median progression-free survival of 7.2 months in patients with dedifferentiated liposarcoma, 100% (22/22) of the patients tested for MDM2 had MDM2 amplification (CN > 6) with a median CN of 28.6 (PMID: 36669146; NCT01877382). | 36669146 |
MDM2 amp | well-differentiated liposarcoma | not applicable | N/A | Clinical Study | Diagnostic | MDM2 amplification aids in the diagnosis of well-differentiated liposarcoma (PMID: 33799733, PMID: 34984861, PMID: 35074968, PMID: 36674856). | 36674856 33799733 34984861 35074968 |
MDM2 amp | dedifferentiated liposarcoma | not applicable | N/A | Clinical Study | Diagnostic | MDM2 amplification aids in the diagnosis of dedifferentiated liposarcoma (PMID: 36674856, PMID: 35074968, PMID: 18500263, PMID: 33799733). | 33799733 36674856 35074968 18500263 |
MDM2 amp | parosteal osteosarcoma | not applicable | N/A | Clinical Study | Diagnostic | MDM2 amplification aids in the diagnosis of parosteal osteosarcoma (PMID: 33799733, PMID: 24786129, PMID: 21336260, PMID: 20601938). | 20601938 33799733 24786129 21336260 |
MDM2 amp | osteosarcoma | sensitive | BI 907828 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, BI 907828 induced tumor regression in a cell line xenograft model of MDM2-amplified osteosarcoma (PMID: 39259562). | 39259562 |