Therapy Detail
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| Therapy Name | Dactolisib + Selumetinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Dactolisib | NVP-BEZ235|BEZ235 | ATR Inhibitor 16 mTOR Inhibitor 51 PI3K Inhibitor (Pan) 42 | Dactolisib (BEZ235) inhibits PI3K kinase, mTOR kinase, and ATR, which may result in tumor cell apoptosis and growth inhibition of tumor cells (PMID: 18606717, PMID: 21552262, PMID: 32088816). | |
| Selumetinib | Koselugo | AZD6244|ARRY-142886 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | Koselugo (selumetinib) inhibits mitogen-activated protein kinase kinases (MEK or MAPK/ERK kinases) 1 and 2, which may prevent the activation of MEK1/2-dependent effector proteins and transcription factors, reducing cellular proliferation in various cancers (PMID: 27467210). Koselugo (selumetinib) is FDA approved for use in pediatric patients of 2 years or older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | Dactolisib + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Koselugo (selumetinib) and BEZ235 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). | 26137449 |
| BRAF L525R | Advanced Solid Tumor | predicted - sensitive | Dactolisib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Dactolisib (BEZ235) to treatment with Koselugo (selumetinib) resulted in increased inhibition of proliferation in Koselugo (selumetinib)-resistant cells expressing BRAF L525R compared to Dactolisib (BEZ235) alone (PMID: 36856908). | 36856908 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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