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Ref Type Journal Article
PMID (23715574)
Authors Bahadoran P, Allegra M, Le Duff F, Long-Mira E, Hofman P, Giacchero D, Passeron T, Lacour JP, Ballotti R
Title Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma.
URL
Abstract Text

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
BRAF L597R missense gain of function BRAF L597R lies within the protein kinase domain of the Braf protein (UniProt.org). L597R results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288, PMID: 26343582), is associated with Erk activation in a patient tumor sample (PMID: 23715574), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF L597R melanoma predicted - sensitive Dabrafenib Preclinical - Patient cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment inhibited Erk activation and reduced viability of patient-derived melanoma cells harboring BRAF L597R 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 L597R melanoma predicted - sensitive Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). 23715574
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 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 L597R melanoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment inhibited growth of skin and lung nodules by 30% and resulted in a duration of response of over 4 months in a melanoma patient harboring BRAF L597R, and inhibited Erk activation and reduced viability of melanoma cells derived from the patient in culture (PMID: 23715574). 23715574