Therapy Detail
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| Therapy Name | PLX4720 + Ponatinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| PLX4720 | PLX-4720|PLX 4720 | BRAF Inhibitor 25 | PLX4720 is a 7-azaindole derivative and RAF kinase inhibitor with greater affinity for BRAF V600E than BRAF wild-type, which may induce cell cycle arrest and apoptosis, and lead to tumor growth inhibition and regression (PMID: 18287029). | |
| Ponatinib | Iclusig | AP24534 | ABL Inhibitor (pan) 9 BCR-ABL Inhibitor 32 DDR1 Inhibitor 10 DDR2 inhibitor 7 FGFR Inhibitor (Pan) 26 FLT3 Inhibitor 69 KIT Inhibitor 57 PDGFR-alpha Inhibitor 9 RET Inhibitor 53 SRC Inhibitor 31 VEGFR Inhibitor (Pan) 36 | Iclusig (ponatinib) inhibits the Bcr-Abl fusion, and other tyrosine kinases, such as RET, DDR, VEGFR, FGFR, KIT, and FLT3 (PMID: 23526464, PMID: 25284748, PMID: 19878872). Iclusig (ponatinib) is FDA-approved for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) as well as ABL1 T315I CML and ABL1 T315I Ph-positive ALL, and in combination with chemotherapy for newly diagnosed Ph-positive ALL (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E | thyroid cancer | sensitive | PLX4720 + Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Iclusig (ponatinib) and PLX4720 treatment demonstrated synergy, and inhibited Erk, Mek, and c-jun phosphorylation, reduced cell proliferation, colony formation, and migration, and induced apoptosis in thyroid cancer cells harboring BRAF V600E and in PLX4720-resistant cells harboring BRAF V600E in culture, and inhibited tumor growth, reduced lung and liver metastases, and increased survival in cell line xenograft models (PMID: 31937621). | 31937621 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|
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