Details

Autor(en) / Beteiligte

• Callahan, Margaret K
• Rampal, Raajit
• Harding, James J
• Klimek, Virginia M
• Chung, Young Rock
• Merghoub, Taha
• Wolchok, Jedd D
• Solit, David B
• Rosen, Neal
• Abdel-Wahab, Omar
• Levine, Ross L
• Chapman, Paul B

Titel

Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

Ist Teil von

• The New England journal of medicine, 2012-12, Vol.367 (24), p.2316-2321

Ort / Verlag

Waltham, MA: Massachusetts Medical Society

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• A man with undiagnosed chronic myelomonocytic leukemia began treatment with vemurafenib for BRAF-mutant metastatic melanoma. His white-cell count soared and then dropped when the drug was withdrawn. The leukemia cells contained an RAS mutation that became more active with RAF inhibition. Approximately 50% of patients with metastatic melanoma harbor a somatic V600E mutation — or, less frequently, a V600K mutation — in the BRAF kinase. 1 – 4 These activating mutations drive increased ERK signaling, promoting the proliferation and survival of melanoma cells. 5 Selective RAF inhibitors, such as vemurafenib and dabrafenib, inhibit ERK signaling and arrest growth in tumors with BRAF V600E or BRAF V600K mutations. 3 , 6 – 8 Treatment with vemurafenib or dabrafenib induces tumor regression in more than half of patients with BRAF V600E–mutant metastatic melanoma. Both drugs also improve the rate of progression-free survival, as compared with dacarbazine. 7 , 9 – 11 Vemurafenib . . .