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Profile Name | TSC2 inact mut |
Gene Variant Detail | |
Relevant Treatment Approaches | mTOR Inhibitor mTORC1 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TSC2 mutant | renal cell carcinoma | conflicting | Everolimus | Clinical Study - Cohort | Actionable | In a retrospective analysis, TSC1, TSC2, or MTOR mutation status was not associated with progression-free survival in renal cell carcinoma patients treated with Afinitor (everolimus) (PMID: 30327302). | 30327302 |
TSC2 mutant | hepatocellular carcinoma | decreased response | Sorafenib | Clinical Study - Cohort | Actionable | In a clinical case study, Nexavar (sorafenib) treatment of patients with hepatocellular carcinoma harboring Mtor pathway mutations in PIK3CA, PTEN, TSC2, or TSC1 (n=12), resulted in a lower disease control rate (8.3% vs. 40.2%), shorter progression-free survival (1.9 months vs. 5.3 months) and shorter overall survival (10.4 months vs. 17.9 months) compared to patients without mutations in this pathway (n=67) (PMID: 30373752; NCT01775072). | 30373752 |
TSC2 mutant | subependymal giant cell astrocytoma | predicted - sensitive | Everolimus | Phase III | Actionable | In a Phase III trial (EXIST-1), Afinitor (everolimus) treatment resulted in a 50% or more tumor reduction in 35% (27/78) of adult and pediatric patients diagnosed with tuberous sclerosis complex and had subependymal giant cell astrocytoma, compared to 0% (0/39) in the placebo group, 85% (99/117) of the patients harbored mutations in TSC1 and/or TSC2 (PMID: 23158522; NCT00789828). | 23158522 |
TSC2 mutant | renal cell carcinoma | conflicting | Everolimus | Case Reports/Case Series | Actionable | In a clinical study, treatment with Afinitor (everolimus) or Torisel (temsirolimus) resulted in more partial responses (odds ratio = 0.08, p=0.030) in patients with renal cell carcinoma harboring mTOR pathway mutations, including MTOR (n=8), TSC1 (n=1), and TSC2 (n=2), than those without mutations (n=76) (PMID: 31335987). | 31335987 |
TSC2 mutant | renal cell carcinoma | predicted - sensitive | Temsirolimus | Case Reports/Case Series | Actionable | In a clinical study, treatment with Afinitor (everolimus) or Torisel (temsirolimus) resulted in more partial responses (odds ratio = 0.08, p=0.030) in patients with renal cell carcinoma harboring mTOR pathway mutations, including MTOR (n=8), TSC1 (n=1), and TSC2 (n=2), than those without mutations (n=76) (PMID: 31335987). | 31335987 |
TSC2 mutant | lung non-small cell carcinoma | no benefit | Vistusertib | Case Reports/Case Series | Actionable | In a Phase II trial (NLMT), Vistusertib (AZD2014) treatment did not result in a confirmed response (0/5) or durable clinical benefit (0/5) in patients with non-small cell lung cancer harboring TSC1 or TSC2 mutations, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). | 32669708 |
TSC2 mutant | osteosarcoma | no benefit | Temsirolimus | Preclinical - Pdx | Actionable | In a preclinical study, Torisel (temsirolimus) treatment did not improve event-free survival in an osteosarcoma patient-derived xenograft (PDX) model harboring a TSC2 mutation (PMID: 37523146). | 37523146 |
TSC2 mutant | osteosarcoma | no benefit | Irinotecan + Temozolomide + Temsirolimus | Case Reports/Case Series | Actionable | In a clinical case study, Torisel (temsirolimus), Temodar (temozolomide), and Camptosar (irinotecan) combination treatment resulted in progressive disease in a pediatric patient with osteosarcoma harboring a TSC2 mutation (PMID: 37523146; NCT03336931). | 37523146 |