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Gene | SMARCB1 |
Variant | negative |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | SMARCB1 negative indicates a lack of the SMARCB1 gene, mRNA, and/or protein. |
Associated Drug Resistance | |
Category Variants Paths |
SMARCB1 mutant SMARCB1 inact mut SMARCB1 negative |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
SMARCB1 negative | rhabdoid cancer | sensitive | Alvocidib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alvocidib (flavopiridol) induced cell-cycle arrest and inhibited growth of human rhabdoid tumor cell lines with SMARCB1 biallelic deficiency in culture and inhibted tumor growth in SMARCB1-deficient cell line xenograft models (PMID: 18223228). | 18223228 |
SMARCB1 negative | rhabdoid cancer | sensitive | Palbociclib | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) inhibited growth of SMARCB1-negative malignant rhabdoid tumor cell lines in culture, and sensitivity was associated with low levels of p16 expression (PMID: 21871868). | 21871868 |
SMARCB1 negative | atypical teratoid rhabdoid tumor | predicted - sensitive | Tazemetostat | Phase I | Actionable | In a Phase I trial, Tazemetostat (EPZ-6438) was well-tolerated and demonstrated anti-tumor activity in pediatric patients with SMARCB1 (INI)-deficient tumors, including complete or partial responses in patients with epithelioid sarcoma (n=1), chordoma (n=2), and atypical teratoid rhaboid tumor (n=1) (AACR-NCI-EORTC Int Conference on Molecular Targets and Cancer Therapeutics 2017, A175; NCT02601937). | detail... |
SMARCB1 negative | chordoma | predicted - sensitive | Tazemetostat | Phase I | Actionable | In a Phase I trial, Tazemetostat (EPZ-6438) was well-tolerated and demonstrated anti-tumor activity in pediatric patients with SMARCB1 (INI)-deficient tumors, including complete or partial responses in patients with epithelioid sarcoma (n=1), chordoma (n=2), and atypical teratoid rhaboid tumor (n=1) (AACR-NCI-EORTC Int Conference on Molecular Targets and Cancer Therapeutics 2017, A175; NCT02601937). | detail... |
SMARCB1 negative | rhabdoid cancer | predicted - sensitive | Tazemetostat | Case Reports/Case Series | Actionable | In a Phase I trial, Tazemetostat (EPZ-6438) demonstrated safety and preliminary efficacy, resulted in a durable complete response lasting over 2.3 years in a patient with SMARCB1-negative malignant rhabdoid tumor (PMID: 29650362; NCT01897571). | 29650362 |
SMARCB1 negative | epithelioid sarcoma | predicted - sensitive | Tazemetostat | Case Reports/Case Series | Actionable | In a Phase I trial, Tazemetostat (EPZ-6438) demonstrated safety and preliminary efficacy, resulted durable stable disease in 2 patients with SMARCB1-negative epithelioid sarcoma (PMID: 29650362; NCT01897571). | 29650362 |
SMARCB1 negative | epithelioid sarcoma | predicted - sensitive | Tazemetostat | Phase I | Actionable | In a Phase I trial, Tazemetostat (EPZ-6438) was well-tolerated and demonstrated anti-tumor activity in pediatric patients with SMARCB1 (INI)-deficient tumors, including complete or partial responses in patients with epithelioid sarcoma (n=1), chordoma (n=2), and atypical teratoid rhaboid tumor (n=1) (AACR-NCI-EORTC Int Conference on Molecular Targets and Cancer Therapeutics 2017, A175; NCT02601937). | detail... |
SMARCB1 negative | epithelioid sarcoma | predicted - sensitive | Tazemetostat | Phase II | Actionable | In a Phase II trial, Tazverik (tazemetostat) treatment resulted in an objective response rate of 15% (9/62) and a disease control rate of 26% (16/62) in patients with locally advanced or metastatic SMARCB1 (INI1)-negative epithelioid sarcoma, with a median duration of response not reached and a median overall survival of 82.4 weeks (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 11003-11003, NCT02601950). | detail... |
SMARCB1 negative | Advanced Solid Tumor | predicted - sensitive | Tazemetostat | Phase I | Actionable | In a Phase I trial, Tazemetostat (EPZ-6438) demonstrated safety and preliminary efficacy, resulted in clinical benefit (stable disease or better) in 38% (5/13) of patients with SMARCB1 or SMARCA4-negative advanced solid tumors (PMID: 29650362; NCT01897571). | 29650362 |
SMARCB1 negative | atypical teratoid rhabdoid tumor | sensitive | DZNeP | Preclinical | Actionable | In a preclinical study, DZNep induced apoptosis and cell-cycle arrest and inhibited growth of SMARCB1-negative atypical teratoid rhabdoid tumor cell lines in culture (PMID: 23190500). | 23190500 |
SMARCB1 negative | rhabdoid cancer | sensitive | Fenretinide + Vorinostat | Preclinical | Actionable | In a preclinical study, the combination of Zolinza (vorinostat) and fenretinide induced apoptosis and inhibited growth of rhabdoid tumor cell lines in culture (PMID: 23764045). | 23764045 |
SMARCB1 negative | atypical teratoid rhabdoid tumor | sensitive | DZNeP + Radiotherapy | Preclinical | Actionable | In a preclinical study, DZNep increased radiosensitivity in SMARCB1-negative atypical teratoid rhabdoid tumor cell lines in culture (PMID: 23190500). | 23190500 |