Details

Autor(en) / Beteiligte

• Vin, Harina
• Ching, Grace
• Ojeda, Sandra S.
• Adelmann, Charles H.
• Chitsazzadeh, Vida
• Dwyer, David W.
• Ma, Haiching
• Ehrenreiter, Karin
• Baccarini, Manuela
• Ruggieri, Rosamaria
• Curry, Jonathan L.
• Ciurea, Ana M.
• Duvic, Madeleine
• Busaidy, Naifa L.
• Tannir, Nizar M.
• Tsai, Kenneth Y.

Titel

Sorafenib suppresses JNK-dependent apoptosis through inhibition of ZAK kinase

Ist Teil von

• Molecular cancer therapeutics, 2013-10, Vol.13 (1), p.221-229

Erscheinungsjahr

2013

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Sorafenib is FDA-approved for the treatment of renal cell carcinoma and hepatocellular carcinoma and has been combined with numerous other targeted therapies and chemotherapies in the treatment of many cancers. Unfortunately, as with other RAF inhibitors, patients treated with sorafenib have a 5–10% rate of developing cutaneous squamous cell carcinoma/keratoacanthomas. Paradoxical activation of ERK in BRAF-wild-type cells has been implicated in RAF-inhibitor-induced cSCC. Here we report that sorafenib suppresses UV-induced apoptosis specifically by inhibiting JNK activation through the off-target inhibition of ZAK kinase. Our results implicate suppression of JNK signaling, independent of the ERK pathway, as an additional mechanism of adverse effects of sorafenib. This has broad implications for combination therapies using sorafenib with other modalities that induce apoptosis.