Predicting the response to sorafenib in hepatocellular carcinoma: where is the evidence for phosphorylated extracellular signaling-regulated kinase (pERK)?
The approval of sorafenib and active development of many other molecularly targeted agents in hepatocellular carcinoma (HCC) have presented a challenge to understand the mechanism of action of sorafenib and identify predictive biomarkers to select patients more likely to benefit from sorafenib. The preclinical study by Zhang and celleagues published this month in BMC Medicine provides preliminary evidence that baseline phosphorylated extracellular signaling-regulated kinase (pERK) may be a relevant marker to reflect the level of constitutive activation of the RAF/mitogen-activated protein kinase kinase (MEK)/ERK signaling pathway and has the potential value in predicting response to sorafenib. The clinical data from the initial single arm phase II study and preliminary report from the randomized phase III study also suggest the correlation of baseline archived tumor pERK levels and time to tumor progression in HCC patients. Whether baseline pERK will prove to be a useful predictive biomarker of response and clinical benefits for sorafenib in HCC will need to be validated in future large prospective studies.
Zhu
Andrew X
AX
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. azhu@partners.org
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D015415:Biomarkers; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases
N Engl J Med. 2008 Jul 24;359(4):378-90
18650514
Mol Cancer Ther. 2008 Oct;7(10):3129-40
18852116
Lancet Oncol. 2009 Jan;10(1):25-34
19095497
Cancer Res. 2006 Dec 15;66(24):11851-8
17178882
Oncogene. 2007 May 14;26(22):3291-310
17496923
Gut. 2003 May;52(5):706-12
12692057
FEBS Lett. 1992 Jul 13;306(1):17-22
1628739
BMC Gastroenterol. 2003 Aug 08;3:19
12906713
Biochem Biophys Res Commun. 1997 Jul 9;236(1):54-8
9223425
J Clin Oncol. 2009 Jun 20;27(18):3027-35
19470923
BMC Med. 2009 Aug 24;7:41
19698189
J Clin Oncol. 2006 Sep 10;24(26):4293-300
16908937
J Am Coll Surg. 2004 Mar;198(3):410-21
14992744
Hepatol Res. 2004 Jun;29(2):113-121
15163433
Clin Cancer Res. 2008 Jun 15;14(12):3651-6
18559577
Cancer Res. 2004 Oct 1;64(19):7099-109
15466206