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Gene | BRAF |
Variant | wild-type |
Impact List | none |
Protein Effect | no effect |
Gene Variant Descriptions | Wild-type BRAF indicates that no mutation has been detected within the BRAF gene. |
Associated Drug Resistance | |
Category Variants Paths |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF wild-type | melanoma | no benefit | Dabrafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 |
BRAF wild-type | melanoma | predicted - sensitive | RAF265 | Phase I | Actionable | In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). | 28719152 |
BRAF wild-type | melanoma | predicted - sensitive | RAF265 | Preclinical | Actionable | In a preclinical study, RAF265 inhibited the growth of melanoma tumors orthotopically implanted in mice, including tumors wild-type for BRAF (PMID: 22351689). | 22351689 |
BRAF wild-type | melanoma | resistant | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 did not inhibit growth of BRAF wild-type melanoma cells in culture or in cell line xenograft models (PMID: 18287029). | 18287029 |
BRAF wild-type | melanoma | no benefit | Selumetinib | Phase II | Actionable | In a Phase II trial, a favorable response rate to Koselugo (selumetinib) was observed in BRAF-mutant, but not BRAF wild-type, melanoma patients (PMID: 22048237). | 22048237 |
BRAF wild-type | melanoma | sensitive | Trametinib | Phase I | Actionable | In a Phase I study, 10% (4/39) of wild-type BRAF melanoma patients had a partial response to Mekinist (trametinib) (PMID: 22805292; NCT00687622). | 22805292 |
BRAF wild-type | thyroid cancer | sensitive | CLM3 | Preclinical | Actionable | In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression, in BRAF wild-type thyroid cancer cells in culture (PMID: 24423321). | 24423321 |
BRAF wild-type | melanoma | resistant | GDC0879 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells in cell culture, cell line xenograft models, and patient-derived xenograft models (PMID: 19276360). | 19276360 |
BRAF wild-type | lung non-small cell carcinoma | resistant | GDC0879 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells in culture and in patient-derived xenograft models (PMID: 19276360). | 19276360 |
BRAF wild-type | Advanced Solid Tumor | no benefit | Lifirafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a variety of BRAF wild-type tumor cell lines were insensitive to Lifirafenib (BGB-283) in culture (PMID: 26208524). | 26208524 |
BRAF wild-type | melanoma | sensitive | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF wild-type melanoma cells demonstrated decreased cell viability when treated with Ibrance (palbociclib) in culture (PMID: 27488531). | 27488531 |
BRAF wild-type | melanoma | decreased response | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a BRAF wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
BRAF wild-type | high grade glioma | predicted - sensitive | Everolimus + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and Selumetinib (AZD6244) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). | 27217440 |
BRAF wild-type | melanoma | predicted - sensitive | Nivolumab | Phase III | Actionable | In a Phase III trial (CheckMate-066), Opdivo (nivolumab) treatment resulted in improved overall survival and response compared to treatment with Deticene (dacarbazine) in melanoma patients with wild-type BRAF, including a 3-year overall survival (OS) rate of 51.2% vs. 21.6%, a median OS of 37.5 months vs. 11.2 months, a complete response in 19% (40/210) vs. 1.4% (3/208), and a partial response in 23.8% (50/210) vs. 13% (27/208), respectively (PMID: 30422243; NCT01721772). | 30422243 |
BRAF wild-type | melanoma | no benefit | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 |
BRAF wild-type | melanoma | predicted - sensitive | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 |
BRAF wild-type | colon cancer | predicted - sensitive | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... |
BRAF wild-type | colon cancer | predicted - sensitive | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... |
BRAF wild-type | rectum cancer | predicted - sensitive | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... |
BRAF wild-type | rectum cancer | predicted - sensitive | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... |