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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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology	31	19	2013 Jul 01	e324-6	J Clin Oncol

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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).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
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
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 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 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

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