Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
| Profile Name | TSC2 inact mut |
| Gene Variant Detail | |
| Relevant Treatment Approaches | mTOR Inhibitor mTORC1 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| TSC2 inact mut | renal cell carcinoma | predicted - sensitive | mTORC1 Inhibitor | Everolimus | Clinical Study - Cohort | Actionable | In a retrospective analysis, 28% (12/43) of metastatic renal cell carcinoma patients who responded to rapalogs, Afinitor (everolimus) or Torisel (temsirolimus), harbored inactivating TSC1, TSC2 mutations and/or activating MTOR mutations, compared to 11% (4/36) in patients who did not respond to therapy (PMID: 26831717). | 26831717 |
| TSC2 inact mut | renal cell carcinoma | predicted - sensitive | mTORC1 Inhibitor | Temsirolimus | Clinical Study - Cohort | Actionable | In a retrospective analysis, 28% (12/43) of metastatic renal cell carcinoma patients who responded to rapalogs, Afinitor (everolimus) or Torisel (temsirolimus), harbored inactivating TSC1, TSC2 mutations and/or activating MTOR mutations, compared to 11% (4/36) in patients who did not respond to therapy (PMID: 26831717). | 26831717 |
| TSC2 inact mut | perivascular epithelioid cell tumor | predicted - sensitive | mTORC1 Inhibitor | Nab-rapamycin | Phase II | Actionable | In a Phase II trial (AMPECT), Fyarro (nab-rapamycin) treatment in patients with perivascular epithelioid cell tumors (PEComas) resulted in partial response in 20% (1/5) of patients with TSC1 mutations, 89% (8/9) of patients with TSC2 mutations, and 9% (1/11) of patients without a TSC1 or TSC2 mutation (PMID: 34637337; NCT02494570). | 34637337 |
| TSC2 inact mut | clear cell renal cell carcinoma | not applicable | N/A | Guideline | Risk Factor | Germline inactivating mutations in TSC2 result in tuberous sclerosis complex (TSC), which is associated with increased risk of developing clear cell renal cell carcinoma (NCCN.org). | detail... | |
| TSC2 inact mut | islet cell tumor | not applicable | N/A | Guideline | Risk Factor | Germline inactivating mutations in TSC2 result in tuberous sclerosis complex (TSC), which is associated with increased risk of developing pancreatic neuroendocrine tumors (NCCN.org). | detail... | |
| TSC2 inact mut | Advanced Solid Tumor | predicted - sensitive | mTORC1 Inhibitor | Nab-rapamycin | Clinical Study | Actionable | In a clinical study, Fyarro (nab-rapamycin) treatment in patients with advanced solid tumors harboring mutations in TSC1 or TSC2 led to a partial response in 4 patients, stable disease in 2 patients and progressive disease in 1 patient of 7 enrolled patients (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3111-3111; NCT03817515). | detail... |
| TSC2 inact mut | transitional cell carcinoma | no benefit | mTOR Inhibitor | Sapanisertib | Phase II | Actionable | In a Phase II trial, treatment with Sapanisertib (MLN0128) in metastatic urothelial carcinoma patients with either a TSC1 or TSC2 activating mutation (n=13) did not result in an objective response and led to a median overall survival of 3.4 months, and the trial was terminated early due to limited clinical activity and poor drug tolerability (Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021) 431-431; NCT03047213). | detail... |
| TSC2 inact mut | Advanced Solid Tumor | no benefit | mTORC1 Inhibitor | Everolimus | Phase II | Actionable | In a Phase II trial, Afinitor (everolimus) treatment resulted in limited activity with an objective response rate of 7% (2/30, 2 partial responses), stable disease in an additional 40% (12/30), a clinical benefit rate of 13% (4/30), a median progression-free survival of 2.3 months, and a median overall survival of 7.3 months in patients with advanced solid tumors harboring inactivating TSC1 or TSC2 mutations or activating MTOR mutations (PMID: 33727259; NCT02201212). | 33727259 |
| TSC2 inact mut | castration-resistant prostate carcinoma | predicted - sensitive | mTOR Inhibitor | CC-115 + Enzalutamide | Phase I | Actionable | In a Phase Ib trial, Xtandi (enzalutamide) plus CC-115 was safe and led to a PSA reduction >= 50% (PSA50) in 80% (32/40) and >=90% (PSA90) in 58% (23/40) of metastatic castration-resistant prostate cancer patients at 12 weeks, and patients with PIK3CA activating mutations or PTEN or TSC1/2 loss of function (n=16) achieved a PSA50, PSA90, and median radiographic progression-free survival of 94%, 63%, and 19.6 mo vs 67%, 47%, and 22.1 mo in PI3K pathway wild-type patients (n=15) (PMID: 37980367; NCT02833883). | 37980367 |
| TSC2 inact mut | Advanced Solid Tumor | no benefit | mTOR Inhibitor | LY3023414 | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-COG Pediatric MATCH), Samotolisib (LY3023414) treatment resulted in no objective responses in pediatric patients with advanced solid tumors harboring PI3K/mTOR pathway mutations, including PTEN (n=6), PIK3CA (n=5), TSC1 (n=2), TSC2 (n=3), and PIK3R1 (n=1), and resulted in a 3-month progression-free survival of 12%, a 6-month overall survival of 44%, and a 12-month overall survival of 15% (PMID: 39298693; NCT03155620). | 39298693 |